1438:
1722:). An analysis of multiple V region sequences by Wu and Kabat identified locations within the V region that were hypervariable and which, they hypothesized, combined in the folded protein to form the antigen recognition site. Thus, within a relatively short time a plausible model was developed for the molecular basis of immunological specificity, and for mediation of biological function through the Fc domain. Crystallization of an IgG molecule soon followed ) confirming the inferences based on sequencing, and providing an understanding of immunological specificity at the highest level of resolution.
1430:
127:
1562:
851:
146:
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1069:. All hormones that act by regulation of gene expression have two consequences in their mechanism of action; their effects are produced after a characteristically long period of time and their effects persist for another long period of time, even after their concentration has been reduced to zero, due to a relatively slow turnover of most enzymes and proteins that would either deactivate or terminate ligand binding onto the receptor.
111:, and so on. Depending on the efficiency of the nodes, a signal can be amplified (a concept known as signal gain), so that one signaling molecule can generate a response involving hundreds to millions of molecules. As with other signals, the transduction of biological signals is characterised by delay, noise, signal feedback and feedforward and interference, which can range from negligible to pathological. With the advent of
704:, the latter permitting the release of second messenger molecules. The total strength of signal amplification by a GPCR is determined by the lifetimes of the ligand-receptor complex and receptor-effector protein complex and the deactivation time of the activated receptor and effectors through intrinsic enzymatic activity; e.g. via protein kinase phosphorylation or b-arrestin-dependent internalization.
874:. Ligand binding to the extracellular domain of integrins changes the protein's conformation, clustering it at the cell membrane to initiate signal transduction. Integrins lack kinase activity; hence, integrin-mediated signal transduction is achieved through a variety of intracellular protein kinases and adaptor molecules, the main coordinator being
1753:
is used. The latter observation was consistent with earlier findings by Fanger et al. These observations tied a biological response to events and structural details of molecules on the cell surface. A preponderance of evidence soon developed that receptor dimerization initiates responses (reviewed in
1762:
and
Perelson who found the size distribution of clusters as a function of time, and its dependence on the affinity and valence of the ligand. Subsequent theories for basophils and mast cells were developed by Goldstein and Sobotka and their collaborators, all aimed at the analysis of dose-response
1355:
Gene activations and metabolism alterations are examples of cellular responses to extracellular stimulation that require signal transduction. Gene activation leads to further cellular effects, since the products of responding genes include instigators of activation; transcription factors produced as
916:
In plants, there are no bona fide integrin receptors identified to date; nevertheless, several integrin-like proteins were proposed based on structural homology with the metazoan receptors. Plants contain integrin-linked kinases that are very similar in their primary structure with the animal ILKs.
695:
Signal transduction by a GPCR begins with an inactive G protein coupled to the receptor; the G protein exists as a heterotrimer consisting of Gα, Gβ, and Gγ subunits. Once the GPCR recognizes a ligand, the conformation of the receptor changes to activate the G protein, causing Gα to bind a molecule
566:
of the inside part of the receptor, a process sometimes called "receptor activation". This results in either the activation of an enzyme domain of the receptor or the exposure of a binding site for other intracellular signaling proteins within the cell, eventually propagating the signal through the
1551:
and allow the passage of only calcium to move through. This causes the cytosolic concentration of
Calcium to increase, causing a cascade of intracellular changes and activity. In addition, calcium and DAG together works to activate PKC, which goes on to phosphorylate other molecules,
1375:
ensues. Such requirements for extracellular stimulation are necessary for controlling cell behavior in unicellular and multicellular organisms; signal transduction pathways are perceived to be so central to biological processes that a large number of diseases are attributed to their dysregulation.
1757:
Such observations led to a number of theoretical (mathematical) developments. The first of these was a simple model proposed by Bell which resolved an apparent paradox: clustering forms stable networks; i.e. binding is essentially irreversible, whereas the affinities of antibodies secreted by B
835:
are structurally distinct from other protein kinases and are found in prokaryotes, fungi, and plants as part of a two-component signal transduction mechanism: a phosphate group from ATP is first added to a histidine residue within the kinase, then transferred to an aspartate residue on a receiver
1733:
has on its surface immunoglobulin receptors whose antigen-binding site is identical to that of antibodies that are secreted by the cell when it encounters an antigen, and more specifically a particular B cell clone secretes antibodies with identical sequences. The final piece of the story, the
402:
and the extracellular medium) is critical for homeostasis. There are three ways in which cells can detect osmotic stimuli: as changes in macromolecular crowding, ionic strength, and changes in the properties of the plasma membrane or cytoskeleton (the latter being a form of mechanotransduction).
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Ligand binding to cell surface receptors is also critical to motility, a phenomenon that is best understood in single-celled organisms. An example is a detection and response to concentration gradients by bacteria -–the classic mathematical theory appearing in. A recent account can be found in
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and a ligand-binding domain; the zinc fingers stabilize DNA binding by holding its phosphate backbone. DNA sequences that match the receptor are usually hexameric repeats of any kind; the sequences are similar but their orientation and distance differentiate them. The ligand-binding domain is
1007:
An example of an ion allowed into the cell during a ligand-gated ion channel opening is Ca; it acts as a second messenger initiating signal transduction cascades and altering the physiology of the responding cell. This results in amplification of the synapse response between synaptic cells by
561:
of the cell, with one part of the receptor on the outside of the cell and the other on the inside. Signal transduction occurs as a result of a ligand binding to the outside region of the receptor (the ligand does not pass through the membrane). Ligand-receptor binding induces a change in the
1191:
First messengers are the signaling molecules (hormones, neurotransmitters, and paracrine/autocrine agents) that reach the cell from the extracellular fluid and bind to their specific receptors. Second messengers are the substances that enter the cytoplasm and act within the cell to trigger a
1695:—were published on the subject. The term first appeared in a paper's title in 1979. Widespread use of the term has been traced to a 1980 review article by Rodbell: Research papers focusing on signal transduction first appeared in large numbers in the late 1980s and early 1990s.
1706:
The purpose of this section is to briefly describe some developments in immunology in the 1960s and 1970s, relevant to the initial stages of transmembrane signal transduction, and how they impacted our understanding of immunology, and ultimately of other areas of cell biology.
696:
of GTP and dissociate from the other two G-protein subunits. The dissociation exposes sites on the subunits that can interact with other molecules. The activated G protein subunits detach from the receptor and initiate signaling from many downstream effector proteins such as
191:
The majority of signal transduction pathways involve the binding of signaling molecules, known as ligands, to receptors that trigger events inside the cell. The binding of a signaling molecule with a receptor causes a change in the conformation of the receptor, known as
1356:
a result of a signal transduction cascade can activate even more genes. Hence, an initial stimulus can trigger the expression of a large number of genes, leading to physiological events like the increased uptake of glucose from the blood stream and the migration of
1303:, which when activated produces another second messenger, cGMP. NO can also act through covalent modification of proteins or their metal co-factors; some have a redox mechanism and are reversible. It is toxic in high concentrations and causes damage during
1247:
that releases more calcium upon binding with it. The nature of calcium in the cytosol means that it is active for only a very short time, meaning its free state concentration is very low and is mostly bound to organelle molecules like
1385:
For example, steroids act directly as transcription factor (gives slow response, as transcription factor must bind DNA, which needs to be transcribed. Produced mRNA needs to be translated, and the produced protein/peptide can undergo
995:
A ligand-gated ion channel, upon binding with a ligand, changes conformation to open a channel in the cell membrane through which ions relaying signals can pass. An example of this mechanism is found in the receiving cell of a neural
927:, has been shown to be a critical element in the plant immune response to signal molecules from bacterial pathogens and plant sensitivity to salt and osmotic stress. ILK1 protein interacts with the high-affinity potassium transporter
1107:
enabling its passage into the nucleus is accessible. Steroid receptors, on the other hand, may be repressive on gene expression when their transactivation domain is hidden. Receptor activity can be enhanced by phosphorylation of
1999:
Bago R, Sommer E, Castel P, Crafter C, Bailey FP, Shpiro N, Baselga J, Cross D, Eyers PA, Alessi DR (2016) The hVps34-SGK3 pathway alleviates sustained PI3K/Akt inhibition by stimulating mTORC1 and tumour growth. EMBO Journal
59:
When signaling pathways interact with one another they form networks, which allow cellular responses to be coordinated, often by combinatorial signaling events. At the molecular level, such responses include changes in the
4639:
Kagey-Sobotka, A, Dembo, M, Goldstein, B, Metzger, H and
Lichtenstein, L M (1981) Qualitative characteristics of histamine release from human basophils by covalently cross-linked IgE. The Journal of Immunology 127 (6),
913:. Epithelial cells (which are non-circulating) normally have active integrins at their cell membrane, helping maintain their stable adhesion to underlying stromal cells that provide signals to maintain normal functioning.
601:
that facilitate signaling protein interactions and coordination of signaling complexes necessary to respond to a particular stimulus. Enzymes and adaptor proteins are both responsive to various second messenger molecules.
1749:(IgE) functions as a surface receptor – degranulate, depends on the concentration of anti IgE antibodies to which they are exposed, and results in a redistribution of surface molecules, which is absent when monovalent
1718:. Biochemical experiments revealed that these so-called Bence Jones proteins consisted of 2 discrete domains –one that varied from one molecule to the next (the V domain) and one that did not (the Fc domain or the
290:
when overexpressed or mutated. This leads to constitutive activation of the pathway, which may or may not be overturned by compensation mechanisms. In the case of HER2, which acts as a dimerization partner of other
3781:
Wilson CH, Ali ES, Scrimgeour N, Martin AM, Hua J, Tallis GA, et al. (March 2015). "Steatosis inhibits liver cell store-operated Ca²⁺ entry and reduces ER Ca²⁺ through a protein kinase C-dependent mechanism".
4583:
Fanger, M W, Hart, D A, Wells, J V, and
Nisonoff, A J (1970) Requirement for cross-linkage in the stimulation of transformation of rabbit peripheral lymphocytes by antiglobulin reagents J. Immun., 105, 1484 -
651:. With nearly 800 members, this is the largest family of membrane proteins and receptors in mammals. Counting all animal species, they add up to over 5000. Mammalian GPCRs are classified into 5 major families:
812:
groups linked to their carboxyl ends. Upon activation, they assign proteins to specific membrane subdomains where they participate in signaling. Activated RTKs in turn activate small G proteins that activate
153:
The basis for signal transduction is the transformation of a certain stimulus into a biochemical signal. The nature of such stimuli can vary widely, ranging from extracellular cues, such as the presence of
4620:
Dembo, M and
Goldstein, B (1978) Theory of equilibrium binding of symmetric bivalent haptens to cell surface antibody: application to histamine release from basophils. The Journal of Immunology 121 (1),
5754:
4546:
Wu, T T, Kabat, E A (1970) An analysis of the sequences of the variable regions of Bence Jones proteins and myeloma light chains and their implications for antibody complementarity. J. Exp. Med. 132:
1046:
and derivatives of vitamins A and D. To initiate signal transduction, the ligand must pass through the plasma membrane by passive diffusion. On binding with the receptor, the ligands pass through the
945:
When activated, toll-like receptors (TLRs) take adapter molecules within the cytoplasm of cells in order to propagate a signal. Four adaptor molecules are known to be involved in signaling, which are
821:. Once activated, these exchange factors can activate more small G proteins, thus amplifying the receptor's initial signal. The mutation of certain RTK genes, as with that of GPCRs, can result in the
782:
are important for signal transduction, either acting downstream of , or as membrane-embedded or cell-soluble versions in their own right. The process of signal transduction involves around 560 known
3624:
Yamamoto M, Sato S, Hemmi H, Uematsu S, Hoshino K, Kaisho T, et al. (November 2003). "TRAM is specifically involved in the Toll-like receptor 4-mediated MyD88-independent signaling pathway".
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to survive. This requirement has led to the development of complex mechanotransduction pathways, allowing cells to sense the stiffness of the substratum. Such signaling is mainly orchestrated in
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Lipophilic second messenger molecules are derived from lipids residing in cellular membranes; enzymes stimulated by activated receptors activate the lipids by modifying them. Examples include
5885:
1134:. These receptors are located in the nucleus and are not accompanied by HSPs. They repress their gene by binding to their specific DNA sequence when no ligand binds to them, and vice versa.
1675:, which strongly influenced the cell's metabolism. Thus, he deduced that the G-protein is a transducer that accepts glucagon molecules and affects the cell. For this, he shared the 1994
4556:
Sarma, V R, Silverton, E W, Davies, D R, Terry W D (1971) The three-dimensional structure at 6 A resolution of a human gamma G1 immunoglobulin molecule, J Biol. Chem. 246 (11) 3752- 9
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or suppression of genes that cause certain responses. Thousands of genes are activated by TLR signaling, implying that this method constitutes an important gateway for gene modulation.
3667:
Yamamoto M, Sato S, Hemmi H, Sanjo H, Uematsu S, Kaisho T, et al. (November 2002). "Essential role for TIRAP in activation of the signalling cascade shared by TLR2 and TLR4".
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Following are some major signaling pathways, demonstrating how ligands binding to their receptors can affect second messengers and eventually result in altered cellular responses.
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Kirsten Jung, Florian
Fabiani, Elisabeth Hoyer, and Jürgen Lassak 2018 Bacterial transmembrane signaling systems and their engineering for biosensing Open Biol. Apr; 8(4): 180023
1259:. The three main pathways that lead to its activation are GPCR pathways, RTK pathways, and gated ion channels; it regulates proteins either directly or by binding to an enzyme.
796:
As is the case with GPCRs, proteins that bind GTP play a major role in signal transduction from the activated RTK into the cell. In this case, the G proteins are members of the
1683:. Thus, the characterization of RTKs and GPCRs led to the formulation of the concept of "signal transduction", a word first used in 1972. Some early articles used the terms
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residues within the intracellular kinase domains of the RTKs, causing conformational changes. Subsequent to this, the receptors' kinase domains are activated, initiating
4851:
4649:
How does T cell receptor clustering impact signal transduction? Jesse
Goyette, Daniel J. Nieves, Yuanqing Ma, Katharina Gaus Journal of Cell Science 2019 132:jcs226423
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Sobotka, A.K. Dembo, M, Goldstein, B and
Lichtenstein, L M, (1979) Antigen-specific desensitization of human basophils The Journal of Immunology, 122 (2) 511-517
4565:
Burnet, F M (1976) A modification of Jerne's theory of antibody production using the concept of clonal selection. CA: A Cancer
Journal for Clinicians 26 (2) 119–21
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are another subset of nuclear receptors. They can be activated by an endocrine-synthesized ligand that entered the cell by diffusion, a ligand synthesised from a
1192:
response. In essence, second messengers serve as chemical relays from the plasma membrane to the cytoplasm, thus carrying out intracellular signal transduction.
901:
are maintained in an inactive state to avoid epithelial cell attachment; they are activated only in response to stimuli such as those received at the site of an
647:
G protein–coupled receptors (GPCRs) are a family of integral transmembrane proteins that possess seven transmembrane domains and are linked to a heterotrimeric
4844:
4574:
Becker, K E, Ishizaka, T, Metzger, H, Ishizaka, K and
Grimley, P M (1973) Surface IgE on Human Basophils during histamine release. J Exp med, 138, 394-408
3028:"Point mutation causing constitutive signaling of CXCR2 leads to transforming activity similar to Kaposi's sarcoma herpesvirus-G protein-coupled receptor"
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are a subclass of nuclear receptors located primarily within the cytosol. In the absence of steroids, they associate in an aporeceptor complex containing
526:
5759:
1004:, such as those that travel along nerves, by depolarizing the membrane of post-synaptic cells, resulting in the opening of voltage-gated ion channels.
978:
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of CXCR2 in an active conformation despite the absence of chemokine-binding. This meant that chemokine receptors can contribute to cancer development.
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region of the genes activated by the hormone-receptor complex. Due to their enabling gene transcription, they are alternatively called inductors of
1860:
Papin JA, Hunter T, Palsson BO, Subramaniam S (February 2005). "Reconstruction of cellular signalling networks and analysis of their properties".
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cells increase as the immune response progresses. A theory of the dynamics of cell surface clustering on lymphocyte membranes was developed by
459:, HSF1 then trimerizes, becoming active and upregulating the expression of its target genes. Many other thermosensory mechanisms exist in both
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MacNab, R., and D. E. Koshland, Jr. (1972). The gradient-sensing mechanism in bacterial chemotaxis. Proc. Natl. Acad. Sci. U.S.A. 69:2509-2512
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Koboldt DC, Fulton RS, McLellan MD, Schmidt H, Kalicki-Veizer J, McMichael JF, et al. (The Cancer Genome Atlas Network) (October 2012).
4593:
Klemm J D, Schreiber S L, Crabtree G R (1998) Ann. Rev. Immunol. Dimerization as a regulatory mechanism in signal transduction 16: 569-592
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of the plasma membrane provided all the ingredients for a new model for the initiation of signal transduction; viz, receptor dimerization.
17:
1034:, are soluble proteins localized within their respective areas. The typical ligands for nuclear receptors are non-polar hormones like the
72:
and conformational changes in proteins, as well as changes in their location. These molecular events are the basic mechanisms controlling
48:, although in some cases the term sensor is used. The changes elicited by ligand binding (or signal sensing) in a receptor give rise to a
1957:
Kolch W, Halasz M, Granovskaya M, Kholodenko BN (September 2015). "The dynamic control of signal transduction networks in cancer cells".
177:. Many other intercellular signal relay mechanisms exist in multicellular organisms, such as those that govern embryonic development.
5355:
4910:
1487:
3510:"Differential binding of calmodulin-related proteins to their targets revealed through high-density Arabidopsis protein microarrays"
3337:
Hehlgans S, Haase M, Cordes N (January 2007). "Signalling via integrins: implications for cell survival and anticancer strategies".
3213:
Reiterer V, Eyers PA, Farhan H (September 2014). "Day of the dead: pseudokinases and pseudophosphatases in physiology and disease".
2372:
Dupont S, Morsut L, Aragona M, Enzo E, Giulitti S, Cordenonsi M, et al. (June 2011). "Role of YAP/TAZ in mechanotransduction".
1403:(EGFR), which causes dimerization and autophosphorylation of the EGFR, which in turn activates the intracellular signaling pathway .
5862:
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5303:
5017:
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87:
Each component (or node) of a signaling pathway is classified according to the role it plays with respect to the initial stimulus.
4772:
5820:
5675:
5216:
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3461:"The Raf-like Kinase ILK1 and the High Affinity K+ Transporter HAK5 Are Required for Innate Immunity and Abiotic Stress Response"
2701:
Shamovsky I, Ivannikov M, Kandel ES, Gershon D, Nudler E (March 2006). "RNA-mediated response to heat shock in mammalian cells".
1589:, were responsible for the release of "internal secretions" with physiological effects. Bernard's "secretions" were later named "
758:; the dimer is stabilized by ligands binding to the receptor. The interaction between the cytoplasmic domains stimulates the auto
597:, the latter controlling the release of intracellular calcium stores into the cytoplasm. Other activated proteins interact with
403:
These changes are detected by proteins known as osmosensors or osmoreceptors. In humans, the best characterised osmosensors are
5698:
5454:
5449:
5211:
4900:
974:
3162:
Manning G, Whyte DB, Martinez R, Hunter T, Sudarsanam S (December 2002). "The protein kinase complement of the human genome".
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cells, most intracellular proteins activated by a ligand/receptor interaction possess an enzymatic activity; examples include
4522:
4131:
3765:
2959:
1941:
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can also mediate mechanotransduction. Specialised forms of mechanotransduction within the nervous system are responsible for
5799:
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3980:
Sako Y, Minoghchi S, Yanagida T (March 2000). "Single-molecule imaging of EGFR signalling on the surface of living cells".
1323:
In addition to nitric oxide, other electronically activated species are also signal-transducing agents in a process called
426:
404:
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patterns of immune cells and their biological correlates. For a recent review of clustering in immunological systems see.
429:. Additionally, animal cells contain a conserved mechanism to prevent high temperatures from causing cellular damage, the
6164:
4314:
Rensing L (1972). "Periodic geophysical and biological signals as Zeitgeber and exogenous inducers in animal organisms".
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The combination of these signals is integrated into altered cytoplasmic machinery which leads to altered cell behaviour.
251:
Not all classifications of signaling molecules take into account the molecular nature of each class member. For example,
4745:
6132:
5842:
1914:
1776:
814:
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belong to a wide range of molecular classes, as do neurotransmitters, which range in size from small molecules such as
4208:
Cowan WM (March 2001). "Viktor Hamburger and Rita Levi-Montalcini: the path to the discovery of nerve growth factor".
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5251:
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Missale C, Nash SR, Robinson SW, Jaber M, Caron MG (January 1998). "Dopamine receptors: from structure to function".
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Important differences exist between integrin-signaling in circulating blood cells and non-circulating cells such as
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Tonndorf J (September 1975). "Davis-1961 revisited. Signal transmission in the cochlear hair cell-nerve junction".
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878:. As shown in the adjacent picture, cooperative integrin-RTK signaling determines the timing of cellular survival,
81:
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Fredriksson R, Schiöth HB (May 2005). "The repertoire of G-protein-coupled receptors in fully sequenced genomes".
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Calcium is used in many processes including muscle contraction, neurotransmitter release from nerve endings, and
660:
69:
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5012:
4988:
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3409:"Arabidopsis NDR1 is an integrin-like protein with a role in fluid loss and plasma membrane-cell wall adhesion"
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leading to altered cellular activity. End-effects include taste, manic depression, tumor promotion, etc.
1532:
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642:
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Rodbell M (March 1980). "The role of hormone receptors and GTP-regulatory proteins in membrane transduction".
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Integrins are produced by a wide variety of cells; they play a role in cell attachment to other cells and the
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897:; integrins of circulating cells are normally inactive. For example, cell membrane integrins on circulating
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to sites of infection. The set of genes and their activation order to certain stimuli is referred to as a
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signaling cascades of downstream cytoplasmic molecules that facilitate various cellular processes such as
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The first hints of this were obtained by Becker et al who demonstrated that the extent to which human
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A Cell Based Immunocytochemical Assay For Monitoring Kinase Signaling Pathways And Drug Efficacy (PDF)
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of signaling pathways and networks has become an essential tool to understand cellular functions and
31:
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DeLisi, C and Perelson A (1976). The kinetics of aggregation phenomena, J. theor. Biol. 62, 159-210
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results in its binding to signaling proteins that are then activated; it is then sequestered in the
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Certain intracellular receptors of the immune system are cytoplasmic receptors; recently identified
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brought to the cell through the bloodstream or a completely intracellularly synthesised ligand like
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residues at their N-terminal as a result of another signal transduction pathway, a process called
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in 1962, led to more detailed insights into the molecular basis of cell signaling, in particular
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61:
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3080:"Role of receptor tyrosine kinase transmembrane domains in cell signaling and human pathologies"
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4466:"Lipid synthesis: an indicator of antigen-induced signal transduction in antigen-binding cells"
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Many adaptor proteins and enzymes activated as part of signal transduction possess specialized
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159:
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Bell, G I (1974) Model for the binding of multivalent antigens to cells, Nature Lond. 248, 430
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Schlessinger J (November 1988). "Signal transduction by allosteric receptor oligomerization".
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Signal Transduction - The Virtual Library of Biochemistry, Molecular Biology and Cell Biology
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that can diffuse through the plasma membrane and affect nearby cells. It is synthesised from
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This article is about signaling at the cellular level. For systemic signal transduction, see
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Delbridge LM, O'Riordan MX (February 2007). "Innate recognition of intracellular bacteria".
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and many other processes. In multicellular organisms, signal transduction pathways regulate
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Beato M, Chávez S, Truss M (April 1996). "Transcriptional regulation by steroid hormones".
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domain on a different protein or the kinase itself, thus activating the aspartate residue.
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of receptors that exist in a constitutively activated state; such mutated genes may act as
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that bind to specific secondary messenger molecules. For example, calcium ions bind to the
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The sensing of temperature in cells is known as thermoception and is primarily mediated by
213:
123:, including signaling rewiring mechanisms underlying responses to acquired drug resistance.
4374:"The effect of N-acylglucosamines on the biosynthesis and secretion of insulin in the rat"
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How to read signal transduction diagrams, what does normal arrow and flathead arrow means.
675:, with a few GPCR groups being difficult to classify due to low sequence similarity, e.g.
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attrition. Traditionally, signals that reach the central nervous system are classified as
8:
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Popescu SC, Popescu GV, Bachan S, Zhang Z, Seay M, Gerstein M, et al. (March 2007).
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is the process by which a chemical or physical signal is transmitted through a cell as a
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Literature-curated human signaling network, the largest human signaling network database
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433:. Such response is triggered when high temperatures cause the dissociation of inactive
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Cascade of intracellular and molecular events for transmission/amplification of signals
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Berg, H C and Purcell, E M (1977) Physics of chemoreception, Biophys. J 20(2):193-219
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Vogelstein B, Kinzler KW (August 2004). "Cancer genes and the pathways they control".
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3853:
3567:
Yamamoto M, Sato S, Hemmi H, Hoshino K, Kaisho T, Sanjo H, et al. (August 2003).
3459:
Brauer EK, Ahsan N, Dale R, Kato N, Coluccio AE, Piñeros MA, et al. (June 2016).
3311:
3284:
2626:
2601:
2179:
2144:
2036:
2011:
1367:
Mammalian cells require stimulation for cell division and survival; in the absence of
1000:. The influx of ions that occurs in response to the opening of these channels induces
6111:
5007:
4963:
4798:
4537:
Steiner, L A (1996) Immunoglobulin evolution, 30 years on. Glycobiology 6 , 649-656
4518:
4487:
4438:
4403:
4354:
4319:
4288:
4225:
4190:
4127:
4120:
4101:
4089:
4054:
3997:
3962:
3921:
3875:
3834:
3799:
3761:
3735:
3692:
3641:
3598:
3549:
3490:
3438:
3389:
3354:
3316:
3301:
3265:
3248:
Roskoski R (June 2004). "The ErbB/HER receptor protein-tyrosine kinases and cancer".
3230:
3187:
3144:
3140:
3109:
3049:
3008:
2955:
2949:
2930:
2873:
2816:
2775:
2726:
2683:
2631:
2582:
2541:
2489:
2438:
2401:
2389:
2354:
2297:
2254:
2219:
2184:
2117:
2113:
2082:
2041:
1974:
1937:
1910:
1877:
1840:
1806:
1332:
1123:
1096:
1092:
1001:
606:
486:
237:
209:
4499:
4450:
4421:
Hildebrand E (April 1977). "What does Halobacterium tell us about photoreception?".
4009:
3704:
3653:
3610:
3569:"Role of adaptor TRIF in the MyD88-independent toll-like receptor signaling pathway"
3199:
3061:
3026:
Burger M, Burger JA, Hoch RC, Oades Z, Takamori H, Schraufstatter IU (August 1999).
2450:
2129:
1986:
1725:
The biological significance of these developments was encapsulated in the theory of
1099:(HSPs). The HSPs are necessary to activate the receptor by assisting the protein to
6237:
6208:
6137:
6033:
5966:
4978:
4956:
4952:
4650:
4477:
4430:
4393:
4385:
4346:
4300:
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4237:
4221:
4217:
4180:
4172:
4081:
4044:
4036:
3989:
3952:
3913:
3865:
3826:
3791:
3727:
3684:
3633:
3588:
3539:
3529:
3480:
3472:
3428:
3420:
3381:
3346:
3306:
3296:
3257:
3222:
3179:
3136:
3099:
3091:
3039:
2998:
2988:
2920:
2912:
2885:
2865:
2806:
2765:
2738:
2718:
2673:
2665:
2621:
2617:
2613:
2572:
2531:
2501:
2481:
2428:
2381:
2344:
2336:
2289:
2272:
Goldstein A (September 1976). "Opioid peptides endorphins in pituitary and brain".
2246:
2211:
2174:
2164:
2109:
2072:
2031:
2023:
1966:
1889:
1869:
1781:
1746:
1726:
1715:
1680:
1609:, were discovered in the following years, the mechanisms remained largely unknown.
1449:
1340:
1276:
1216:. Two combined receptor/ion channel proteins control the transport of calcium: the
1088:
1047:
1027:
1009:
832:
583:
391:
373:
357:
233:
104:
4023:
Orton RJ, Sturm OE, Vyshemirsky V, Calder M, Gilbert DR, Kolch W (December 2005).
3957:
3940:
2250:
6116:
5693:
5425:
5420:
5386:
5283:
5035:
4810:
4794:
4776:
4762:
4749:
4708:
4703:
3385:
2770:
2753:
1711:
1598:
1594:
1540:
1508:
1493:
1361:
1336:
1324:
1307:, but is the cause of many other functions like the relaxation of blood vessels,
1100:
1082:
1066:
894:
822:
805:
797:
783:
779:
767:
759:
755:
720:
575:
558:
490:
326:
276:
196:. Most ligands are soluble molecules from the extracellular medium which bind to
116:
4482:
4465:
4025:"Computational modelling of the receptor-tyrosine-kinase-activated MAPK pathway"
3350:
3044:
3027:
866:
and in the transduction of signals from extracellular matrix components such as
582:. Often such enzymes are covalently linked to the receptor. Some of them create
6303:
6249:
6056:
5926:
5397:
3514:
Proceedings of the National Academy of Sciences of the United States of America
3261:
2149:
Proceedings of the National Academy of Sciences of the United States of America
1791:
1692:
1660:
1574:
1457:
1256:
1104:
850:
708:
408:
369:
201:
126:
3731:
3285:"Histidine protein kinases: key signal transducers outside the animal kingdom"
3226:
2834:
2811:
2794:
2754:"Beyond counting photons: trials and trends in vertebrate visual transduction"
2669:
2077:
2060:
411:
of human cells. In yeast, the HOG pathway has been extensively characterised.
6313:
6051:
5415:
5288:
4176:
2993:
2977:"Mechanisms of regulation and function of G-protein-coupled receptor kinases"
2901:"Inactive-state preassembly of G(q)-coupled receptors and G(q) heterotrimers"
1931:
1629:
1586:
1582:
1469:
1453:
1368:
1174:
1131:
1078:
751:
743:
697:
681:
664:
542:
538:
420:
322:
260:
236:
are lipid-soluble and thus cross the plasma membrane to reach cytoplasmic or
5476:
4719:
3917:
3593:
3568:
3534:
3183:
2464:
Kung C (August 2005). "A possible unifying principle for mechanosensation".
2169:
1714:
light chains, which are found in abundance in the urine of individuals with
1573:
The earliest notion of signal transduction can be traced back to 1855, when
854:
An overview of integrin-mediated signal transduction, adapted from Hehlgens
6276:
6041:
6037:
5432:
5270:
4229:
4194:
4093:
4058:
4001:
3966:
3838:
3803:
3739:
3696:
3645:
3602:
3553:
3494:
3442:
3393:
3358:
3320:
3269:
3234:
3191:
3113:
3053:
3012:
2934:
2877:
2869:
2820:
2779:
2730:
2687:
2635:
2586:
2577:
2560:
2545:
2536:
2519:
2493:
2442:
2393:
2358:
2293:
2223:
2202:
Ronnett GV, Moon C (2002). "G proteins and olfactory signal transduction".
2188:
2086:
2045:
2027:
1978:
1881:
1786:
1501:
1468:
components. In many cell types, activation of this pathway promotes
1288:
1249:
1213:
1051:
1043:
1039:
902:
726:
701:
518:
385:
337:
130:
Simplified representation of major signal transduction pathways in mammals.
4323:
4292:
3925:
3879:
3424:
3148:
2433:
2416:
2258:
2121:
6271:
6084:
5335:
4905:
4818:
4491:
4442:
4407:
4358:
2916:
2301:
1357:
1343:. Redox signaling also includes active modulation of electronic flows in
1268:
1073:
883:
867:
579:
460:
268:
217:
73:
3688:
3476:
2722:
2485:
2385:
2340:
6224:
5525:
5320:
4997:
4654:
4434:
4040:
3854:"Signal transduction and gene regulation: the nuclear response to cAMP"
3817:
Forman HJ (November 2009). "Signal transduction and reactive species".
3795:
2012:"Different telomere damage signaling pathways in human and mouse cells"
1700:
1637:
1328:
1142:
910:
898:
775:
672:
614:
587:
522:
514:
464:
395:
264:
221:
77:
4787:
4697:
Netpath - A curated resource of signal transduction pathways in humans
4389:
3095:
145:
6254:
5988:
5847:
5789:
5002:
4920:
4284:
3993:
3372:
Gilcrease MZ (March 2007). "Integrin signaling in epithelial cells".
2417:"Cellular mechanotransduction: putting all the pieces together again"
1742:
1672:
1649:
1645:
1372:
1308:
1236:
1031:
906:
905:. In a similar manner, integrins at the cell membrane of circulating
879:
826:
809:
712:
648:
571:
510:
506:
318:
225:
205:
4742:
1970:
1873:
1452:: A pathway that couples intracellular responses to the binding of
958:
6298:
6046:
4085:
2520:"Osmosensory mechanisms in cellular and systemic volume regulation"
1664:
1602:
1590:
1312:
1292:
1272:
1233:
1170:
1081:
of nucleic receptors prior to binding and providing structures for
1057:
Activated nuclear receptors attach to the DNA at receptor-specific
871:
845:
763:
668:
353:
349:
330:
256:
252:
162:
3637:
1158:
808:. They act as molecular switches usually tethered to membranes by
267:. Moreover, some molecules may fit into more than one class, e.g.
44:. Proteins responsible for detecting stimuli are generally termed
6028:
5867:
5591:
5437:
4866:
1606:
1566:
1548:
1524:
1465:
1205:
1166:
1127:
1035:
997:
747:
610:
399:
361:
158:, to intracellular events, such as the DNA damage resulting from
120:
4782:
4463:
1956:
1691:. In 2007, a total of 48,377 scientific papers—including 11,211
961:. These adapters activate other intracellular molecules such as
103:. Such effectors are typically proteins and are often linked to
5872:
5660:
5655:
5365:
4464:
Kenny JJ, Martínez-Maza O, Fehniger T, Ashman RF (April 1979).
2700:
1759:
1750:
1730:
1578:
1473:
1304:
1109:
791:
739:
735:
502:
296:
170:
4755:
5886:
deficiencies of intracellular signaling peptides and proteins
5670:
5665:
5627:
5612:
5579:
5574:
5535:
5530:
5518:
5513:
5508:
5503:
5491:
5469:
5464:
5459:
5236:
5231:
5226:
5221:
5181:
5176:
5114:
5109:
5104:
5099:
5074:
5069:
5064:
5059:
5054:
5049:
5044:
1859:
1671:
disassociated glucagon from this receptor and stimulated the
1486:) (see picture), and, thus, further effects depend mainly on
1482:: In humans, cAMP works by activating protein kinase A (PKA,
1287:
Nitric oxide (NO) acts as a second messenger because it is a
1162:
1154:
966:
962:
950:
946:
482:
453:
449:
445:
441:
365:
334:
166:
2314:
5852:
5837:
5622:
5562:
5557:
5552:
5547:
5486:
5481:
5325:
5298:
5293:
5206:
5201:
5196:
5191:
5186:
5163:
5158:
5153:
5148:
5143:
5094:
5089:
5079:
4814:
4022:
2317:"Comprehensive molecular portraits of human breast tumours"
1150:
954:
928:
818:
434:
341:
292:
283:
229:
4696:
3161:
2061:"Mosaic and regulative development: two faces of one coin"
1149:(LRR) motif similar to TLRs. Some of these molecules like
295:, constitutive activation leads to hyperproliferation and
3780:
3507:
1085:
used for communication with the translational apparatus.
630:
537:
Receptors can be roughly divided into two major classes:
498:
5925:
4765:- Signal transduction pathway mining in PubMed abstracts
4371:
4118:
Alberts B, Lewis J, Raff M, Roberts K, Walter P (2002).
3623:
3566:
2947:
2236:
1839:(2nd ed.). Amsterdam, Netherlands: Academic Press.
1464:. This pathway is very complex and includes many
734:(RTKs) are transmembrane proteins with an intracellular
727:
Tyrosine, Ser/Thr and Histidine-specific protein kinases
4117:
3339:
Biochimica et Biophysica Acta (BBA) - Reviews on Cancer
2602:"Osmotic stress signaling and osmoadaptation in yeasts"
2371:
1667:
on a rat's liver cell membrane receptor. He noted that
1644:
to include only signaling from glands, while the terms
149:
3D Medical animation still showing signal transduction.
3717:
3666:
2145:"The further redefining of steroid-mediated signaling"
1072:
Nucleic receptors have DNA-binding domains containing
340:
detects changes and transmits them downstream through
6287:
3979:
3025:
2517:
1656:, while Levi-Montalcini and Cohen shared it in 1986.
625:
and other phosphoinositides do the same thing to the
232:, respectively). In addition, some molecules such as
4512:
4372:
Ashcroft SJ, Crossley JR, Crossley PC (March 1976).
3755:
3283:
Wolanin PM, Thomason PA, Stock JB (September 2002).
3282:
2518:
Pedersen SF, Kapus A, Hoffmann EK (September 2011).
2009:
1698:
1605:
in 1902. Although many other hormones, most notably
750:. To perform signal transduction, RTKs need to form
52:, which is a chain of biochemical events known as a
3458:
3454:
3452:
3336:
3250:
Biochemical and Biophysical Research Communications
3212:
2795:"Phototransduction in ganglion-cell photoreceptors"
1519:). DAG remains bound to the membrane, and IP
977:that amplify the signal, eventually leading to the
527:
intrinsically photosensitive retinal ganglion cells
5760:Sh2 domain-containing protein tyrosine phosphatase
4723:s STKE - Signal Transduction Knowledge Environment
4119:
3896:Rosen OM (September 1987). "After insulin binds".
3851:
2948:Berg JM, Tymoczko JL, Stryer L, Clarke ND (2002).
2855:
1906:Biochemistry of Signal Transduction and Regulation
1754:) in a variety of cell types, including B cells.
1652:began to be used. Sutherland was awarded the 1971
1441:Elements of Signal transduction cascade networking
517:. In the case of the circadian clock, a different
4071:
1710:The relevant events begin with the sequencing of
679:. Other classes exist in eukaryotes, such as the
6311:
3449:
3406:
3120:
2898:
2099:
1565:Occurrence of the term "signal transduction" in
804:, and Raf families, referred to collectively as
4716:- A database about signal transduction pathways
2899:Qin K, Dong C, Wu G, Lambert NA (August 2011).
2651:
1376:Three basic signals determine cellular growth:
3760:(7th ed.). McGraw-Hill. pp. 159–60.
3751:
3749:
3617:
3560:
2751:
2058:
1834:
1224:that transports calcium upon interaction with
738:domain and an extracellular domain that binds
636:
505:. In the case of vision, light is detected by
5911:
4868:Intracellular signaling peptides and proteins
4852:
3938:
3660:
2892:
2565:Journal of the American Society of Nephrology
2524:Journal of the American Society of Nephrology
1929:
1531:then diffuses through the cytosol to bind to
3206:
3155:
3126:
1547:(ER). These channels are specific to
1523:is released as a soluble structure into the
1275:, the former required for the activation of
984:
244:, their stimulation leads to binding to the
4126:(4th ed.). New York: Garland Science.
3810:
3746:
3332:
3330:
2835:"A molecular model for receptor activation"
2647:
2645:
2513:
2511:
2201:
923:, one of the integrin-linked kinase genes,
271:is a neurotransmitter when secreted by the
5918:
5904:
5755:Receptor-like protein tyrosine phosphatase
4859:
4845:
4779:Analytical Biochemistry 338 (2005) 136-142
4513:Gomperts BD, Kramer IM, Tatham PE (2002).
4420:
4414:
4258:
4256:
4113:
4111:
3077:
2606:Microbiology and Molecular Biology Reviews
2010:Smogorzewska A, de Lange T (August 2002).
1577:proposed that ductless glands such as the
1015:
715:receptor CXCR2; mutated cells underwent a
557:and make up most receptors. They span the
548:
493:by activating light-sensitive proteins in
5356:Cyclin-dependent kinase inhibitor protein
4735:at the U.S. National Library of Medicine
4481:
4397:
4184:
4048:
4016:
3956:
3869:
3592:
3543:
3533:
3484:
3432:
3371:
3365:
3310:
3300:
3103:
3073:
3071:
3043:
3002:
2992:
2924:
2810:
2769:
2677:
2625:
2576:
2535:
2432:
2348:
2271:
2265:
2178:
2168:
2076:
2035:
5863:Phosphatidylethanolamine binding protein
5499:Interleukin-1 receptor associated kinase
4911:Ca2+/calmodulin-dependent protein kinase
4506:
4365:
4336:
4330:
3932:
3891:
3889:
3756:Vander AJ, Sherman J, Luciano D (1998).
3407:Knepper C, Savory EA, Day B (May 2011).
3327:
3247:
3241:
2851:
2849:
2847:
2752:Burns ME, Arshavsky VY (November 2005).
2642:
2558:
2508:
2216:10.1146/annurev.physiol.64.082701.102219
1560:
1436:
1428:
1145:cells and interact with ligands using a
849:
711:was inserted into the gene encoding the
525:, is responsible for detecting light in
144:
125:
4316:International Journal of Biometeorology
4313:
4307:
4262:
4253:
4145:
4143:
4108:
2974:
2599:
2230:
2195:
1923:
1490:, which vary based on the type of cell.
1141:(NLRs) reside in the cytoplasm of some
629:of proteins such as the kinase protein
14:
6312:
5618:Focal adhesion protein-tyrosine kinase
4901:Intracellular calcium-sensing proteins
3852:Lalli E, Sassone-Corsi P (July 1994).
3816:
3068:
3019:
2792:
2561:"How does the brain sense osmolality?"
2414:
2142:
2136:
1902:
1862:Nature Reviews. Molecular Cell Biology
1640:in 1956, prompted the redefinition of
1476:are associated with aberrations in it.
1169:and initiate processing of particular
934:
5899:
4840:
4457:
4423:Biophysics of Structure and Mechanism
4207:
3895:
3886:
3845:
2844:
2745:
1835:Bradshaw RA, Dennis EA, eds. (2010).
1677:Nobel Prize in Physiology or Medicine
1654:Nobel Prize in Physiology or Medicine
1505:phosphatidylinositol 4,5-bisphosphate
1411:Permissive (cell-matrix interactions)
1350:
1200:The release of calcium ions from the
427:transient receptor potential channels
405:transient receptor potential channels
4351:10.1001/archotol.1975.00780380006002
4244:
4158:
4140:
3973:
2652:Sengupta P, Garrity P (April 2013).
2463:
2093:
2059:Lawrence PA, Levine M (April 2006).
1936:. San Francisco: Benjamin Cummings.
1180:
909:are normally kept inactive to avoid
778:. Many Ser/Thr and dual-specificity
302:
6165:Transcription preinitiation complex
3858:The Journal of Biological Chemistry
3831:10.1016/j.freeradbiomed.2009.09.002
3819:Free Radical Biology & Medicine
1262:
815:guanine nucleotide exchange factors
617:, allowing it to bind and activate
321:means that most cell types require
275:and a hormone when secreted by the
24:
6133:Signal transducing adaptor protein
5843:Signal transducing adaptor protein
5018:3',5'-cyclic-GMP phosphodiesterase
4974:3',5'-cyclic-AMP phosphodiesterase
4250:Bradshaw & Dennis (2010) p. 2.
4149:Bradshaw & Dennis (2010) p. 1.
1393:Transcription independent response
1318:
931:and with the calcium sensor CML9.
833:Histidine-specific protein kinases
25:
6346:
5838:Activating transcription factor 6
5252:G protein-coupled receptor kinase
4804:Cell cycle - Homo sapiens (human)
4690:
3939:Massagué J, Gomis RR (May 2006).
1418:
1026:Intracellular receptors, such as
690:fungal mating pheromone receptors
390:Cellular and systemic control of
224:can also bind to such receptors (
6297:
5382:Phosphoinositide phospholipase C
3941:"The logic of TGFbeta signaling"
3302:10.1186/gb-2002-3-10-reviews3013
1401:epidermal growth factor receptor
1383:Transcription dependent response
1299:and works through activation of
1061:(HRE) sequences, located in the
917:In the experimental model plant
4678:
4669:
4660:
4643:
4633:
4624:
4614:
4605:
4596:
4587:
4577:
4568:
4559:
4550:
4540:
4531:
4201:
4161:"One hundred years of hormones"
4152:
4065:
3774:
3711:
3501:
3400:
3276:
2968:
2954:. San Francisco: W.H. Freeman.
2941:
2827:
2786:
2694:
2593:
2552:
2457:
2408:
2365:
2308:
1817:Two-component regulatory system
1282:
1228:on its cytosolic side; and the
1161:signaling, whereas others like
555:integral transmembrane proteins
5821:GTP-binding protein regulators
5811:GTP-binding protein regulators
4752:, from Nature Publishing Group
4222:10.1146/annurev.neuro.24.1.551
3129:Trends in Biochemical Sciences
2618:10.1128/MMBR.66.2.300-372.2002
2052:
2003:
1993:
1950:
1896:
1853:
1828:
1720:Fragment crystallizable region
1408:Inhibitory (cell-cell contact)
1388:posttranslational modification
707:A study was conducted where a
414:
173:to neuron in a process called
13:
1:
5570:Rho-associated protein kinase
4743:UCSD-Nature Signaling Gateway
4210:Annual Review of Neuroscience
4122:Molecular biology of the cell
3958:10.1016/j.febslet.2006.04.033
3871:10.1016/S0021-9258(17)32442-0
3720:Current Opinion in Immunology
3078:Li E, Hristova K (May 2006).
2559:Verbalis JG (December 2007).
2251:10.1152/physrev.1998.78.1.189
1822:
1488:cAMP-dependent protein kinase
1484:cAMP-dependent protein kinase
1380:Stimulatory (growth factors)
1077:additionally responsible for
379:
288:ligand-independent activation
248:of steroid-responsive genes.
169:. These are transmitted from
5776:Dual-specificity phosphatase
5751:protein tyrosine phosphatase
5257:AMP-activated protein kinase
4823:Pathway Interaction Database
3386:10.1016/j.canlet.2006.03.031
3141:10.1016/0968-0004(88)90219-8
2771:10.1016/j.neuron.2005.10.014
2114:10.1016/0039-128X(96)00030-X
1930:Reece J, Campbell N (2002).
1632:. Their work, together with
1210:smooth endoplasmic reticulum
1054:, altering gene expression.
839:
553:Extracellular receptors are
532:
18:Signal transduction pathways
7:
5800:apoptosis signaling pathway
4483:10.4049/jimmunol.122.4.1278
3351:10.1016/j.bbcan.2006.09.001
3045:10.4049/jimmunol.163.4.2017
2204:Annual Review of Physiology
1812:Protein–protein interaction
1770:
1513:inositol 1,4,5-triphosphate
1425:List of signalling pathways
1347:biological macromolecules.
1165:interact with inflammatory
637:G protein–coupled receptors
627:Pleckstrin homology domains
619:calmodulin-dependent kinase
84:in a wide variety of ways.
10:
6351:
4788:Signaling PAthway Database
4657:Published 11 February 2019
4339:Archives of Otolaryngology
3262:10.1016/j.bbrc.2004.04.150
1837:Handbook of Cell Signaling
1601:, Starling had discovered
1569:-indexed papers since 1977
1556:
1422:
1195:
1184:
1059:hormone-responsive element
1019:
988:
938:
843:
643:G protein–coupled receptor
640:
474:
418:
383:
306:
184:
180:
138:
134:
95:, while receptors are the
42:series of molecular events
29:
6217:
6187:
6150:
6125:
6102:
6093:
6065:
6019:
6012:
5937:
5881:
5830:
5809:
5788:
5768:
5740:
5721:
5711:
5686:
5644:Serine/threonine/tyrosine
5643:
5602:
5405:
5395:
5374:
5348:
5269:
5247:
5130:
5031:
4987:
4937:
4928:
4919:
4893:
4874:
3732:10.1016/j.coi.2006.11.005
3227:10.1016/j.tcb.2014.03.008
2812:10.1007/s00424-007-0242-2
2793:Berson DM (August 2007).
2670:10.1016/j.cub.2013.03.009
2078:10.1016/j.cub.2006.03.016
1909:. Wiley-VCH. p. 15.
1012:involved in the synapse.
985:Ligand-gated ion channels
732:Receptor tyrosine kinases
242:steroid hormone receptors
32:Transduction (physiology)
6245:Neuroendocrine signaling
5858:Olfactory marker protein
5445:Glycogen synthase kinase
4948:Heterotrimeric G protein
4737:Medical Subject Headings
4177:10.1038/sj.embor.7400444
2994:10.3748/wjg.v12.i48.7753
2143:Hammes SR (March 2003).
1663:examined the effects of
1301:soluble guanylyl cyclase
991:Ligand-gated ion channel
717:malignant transformation
477:Visual phototransduction
470:
5651:Dual-specificity kinase
5361:Cyclin-dependent kinase
4378:The Biochemical Journal
4029:The Biochemical Journal
3918:10.1126/science.2442814
3784:The Biochemical Journal
3594:10.1126/science.1087262
3535:10.1073/pnas.0611615104
3184:10.1126/science.1075762
2905:Nature Chemical Biology
2600:Hohmann S (June 2002).
2170:10.1073/pnas.0530224100
1797:Gene regulatory network
1699:Signal transduction in
1622:epidermal growth factor
1597:in 1905. Together with
1397:epidermal growth factor
1187:Second messenger system
1120:Retinoic acid receptors
1103:in a way such that the
1016:Intracellular receptors
790:, encoded by the human
549:Extracellular receptors
346:cell adhesion molecules
282:Some receptors such as
6107:cAMP-dependent pathway
4783:www.Redoxsignaling.com
3215:Trends in Cell Biology
2975:Yang W, Xia S (2006).
2870:10.1124/mol.104.009001
2858:Molecular Pharmacology
2578:10.1681/ASN.2007070825
2537:10.1681/ASN.2010121284
2415:Ingber DE (May 2006).
2294:10.1126/science.959823
1959:Nature Reviews. Cancer
1669:guanosine triphosphate
1634:Earl Wilbur Sutherland
1570:
1480:cAMP-dependent pathway
1442:
1434:
1243:receptor but having a
1022:Intracellular receptor
876:integrin-linked kinase
859:
746:receptors such as the
661:metabotropic glutamate
485:controls the sense of
273:central nervous system
198:cell surface receptors
150:
131:
99:, which then activate
6233:Synaptic transmission
6229:Neurocrine signaling
6152:Transcription factors
5999:PI3K/AKT/mTOR pathway
5732:Protein phosphatase 2
5543:p21-activated kinases
4768:Huaxian Chen, et al.
4470:Journal of Immunology
4159:Tata JR (June 2005).
3425:10.1104/pp.110.169656
3032:Journal of Immunology
2981:World J Gastroenterol
2654:"Sensing temperature"
2434:10.1096/fj.05-5424rev
2239:Physiological Reviews
1564:
1545:endoplasmic reticulum
1440:
1432:
1423:Further information:
1239:, similar to the InsP
1226:inositol triphosphate
1202:endoplasmic reticulum
1032:cytoplasmic receptors
903:inflammatory response
853:
677:vomeronasal receptors
452:. With help from the
187:Ligand (biochemistry)
175:synaptic transmission
148:
141:Stimulus (physiology)
129:
113:computational biology
107:, which can activate
5135:G beta-gamma complex
4729:, published by AAAS.
4318:. 16 Suppl: 113–25.
2917:10.1038/nchembio.642
2028:10.1093/emboj/cdf433
1745:—for which bivalent
1689:sensory transduction
1618:Rita Levi-Montalcini
1472:, and many forms of
920:Arabidopsis thaliana
864:extracellular matrix
772:cell differentiation
686:cyclic AMP receptors
437:from complexes with
344:. Calcium-dependent
329:, regions where the
214:extracellular matrix
212:. Components of the
6320:Signal transduction
6262:Mechanotransduction
6250:Exocrine signalling
6057:Signaling molecules
5931:Signal transduction
5714:protein phosphatase
5587:Ribosomal s6 kinase
4733:Signal+Transduction
4725:, from the journal
4515:Signal transduction
4277:1980Natur.284...17R
3982:Nature Cell Biology
3910:1987Sci...237.1452R
3689:10.1038/nature01182
3681:2002Natur.420..324Y
3585:2003Sci...301..640Y
3526:2007PNAS..104.4730P
3477:10.1104/pp.16.00035
3295:(10): REVIEWS3013.
3176:2002Sci...298.1912M
2723:10.1038/nature04518
2715:2006Natur.440..556S
2486:10.1038/nature03896
2478:2005Natur.436..647K
2386:10.1038/nature10137
2341:10.1038/nature11412
2333:2012Natur.490...61T
2286:1976Sci...193.1081G
2161:2003PNAS..100.2168H
1802:Hormonal imprinting
1729:which holds that a
1685:signal transmission
1642:endocrine signaling
1614:nerve growth factor
1327:. Examples include
1147:leucine-rich repeat
935:Toll-like receptors
742:; examples include
495:photoreceptor cells
439:heat shock proteins
431:heat-shock response
394:(the difference in
309:Mechanotransduction
194:receptor activation
109:secondary effectors
50:biochemical cascade
38:Signal transduction
6272:Ion channel gating
6004:Integrin receptors
5938:Signaling pathways
4884:MAP kinase pathway
4809:2012-10-23 at the
4793:2012-09-17 at the
4775:2012-02-22 at the
4761:2019-05-11 at the
4748:2013-02-12 at the
4702:2012-09-20 at the
4655:10.1242/jcs.226423
4517:. Academic Press.
4435:10.1007/BF00536457
4041:10.1042/BJ20050908
3796:10.1042/bj20140881
1736:Fluid mosaic model
1571:
1500:: PLC cleaves the
1443:
1435:
1351:Cellular responses
1295:and oxygen by the
1245:feedback mechanism
1230:ryanodine receptor
1139:NOD-like receptors
1097:heatshock proteins
941:Toll-like receptor
860:
317:in the tissues of
315:basement membranes
313:The prevalence of
151:
132:
97:signal transducers
82:cell communication
70:post-translational
6285:
6284:
6267:Phototransduction
6225:Intracrine action
6183:
6182:
6146:
6145:
6034:Neurotransmitters
5893:
5892:
5848:I-kappa B protein
5784:
5783:
5707:
5706:
5344:
5343:
5265:
5264:
5008:Guanylate cyclase
4964:Adenylate cyclase
4799:Kyushu University
4524:978-0-12-289631-6
4390:10.1042/bj1540701
4133:978-0-8153-3218-3
3767:978-0-07-067065-5
3626:Nature Immunology
3170:(5600): 1912–34.
3096:10.1021/bi060609y
2961:978-0-7167-4954-7
1943:978-0-8053-6624-2
1903:Krauss G (2008).
1807:Metabolic pathway
1612:The discovery of
1507:(PIP2), yielding
1333:hydrogen peroxide
1181:Second messengers
1089:Steroid receptors
1028:nuclear receptors
1002:action potentials
584:second messengers
303:Mechanical forces
240:. In the case of
238:nuclear receptors
210:neurotransmitters
105:second messengers
101:primary effectors
76:, proliferation,
54:signaling pathway
16:(Redirected from
6342:
6302:
6301:
6293:
6238:Chemical synapse
6138:Scaffold protein
6100:
6099:
6095:Second messenger
6021:Receptor ligands
6017:
6016:
5920:
5913:
5906:
5897:
5896:
5723:Serine/threonine
5719:
5718:
5407:Serine/threonine
5403:
5402:
5023:Protein kinase G
4979:Protein kinase A
4935:
4934:
4926:
4925:
4861:
4854:
4847:
4838:
4837:
4685:
4682:
4676:
4673:
4667:
4664:
4658:
4647:
4641:
4637:
4631:
4628:
4622:
4618:
4612:
4609:
4603:
4600:
4594:
4591:
4585:
4581:
4575:
4572:
4566:
4563:
4557:
4554:
4548:
4544:
4538:
4535:
4529:
4528:
4510:
4504:
4503:
4485:
4461:
4455:
4454:
4418:
4412:
4411:
4401:
4369:
4363:
4362:
4334:
4328:
4327:
4311:
4305:
4304:
4285:10.1038/284017a0
4260:
4251:
4248:
4242:
4241:
4205:
4199:
4198:
4188:
4156:
4150:
4147:
4138:
4137:
4125:
4115:
4106:
4105:
4069:
4063:
4062:
4052:
4035:(Pt 2): 249–61.
4020:
4014:
4013:
3994:10.1038/35004044
3977:
3971:
3970:
3960:
3936:
3930:
3929:
3904:(4821): 1452–8.
3893:
3884:
3883:
3873:
3864:(26): 17359–62.
3849:
3843:
3842:
3814:
3808:
3807:
3778:
3772:
3771:
3758:Human Physiology
3753:
3744:
3743:
3715:
3709:
3708:
3664:
3658:
3657:
3621:
3615:
3614:
3596:
3564:
3558:
3557:
3547:
3537:
3505:
3499:
3498:
3488:
3465:Plant Physiology
3456:
3447:
3446:
3436:
3413:Plant Physiology
3404:
3398:
3397:
3369:
3363:
3362:
3334:
3325:
3324:
3314:
3304:
3280:
3274:
3273:
3245:
3239:
3238:
3210:
3204:
3203:
3159:
3153:
3152:
3124:
3118:
3117:
3107:
3075:
3066:
3065:
3047:
3023:
3017:
3016:
3006:
2996:
2972:
2966:
2965:
2945:
2939:
2938:
2928:
2896:
2890:
2889:
2853:
2842:
2841:
2839:
2831:
2825:
2824:
2814:
2790:
2784:
2783:
2773:
2749:
2743:
2742:
2709:(7083): 556–60.
2698:
2692:
2691:
2681:
2649:
2640:
2639:
2629:
2597:
2591:
2590:
2580:
2556:
2550:
2549:
2539:
2515:
2506:
2505:
2472:(7051): 647–54.
2461:
2455:
2454:
2436:
2412:
2406:
2405:
2380:(7350): 179–83.
2369:
2363:
2362:
2352:
2312:
2306:
2305:
2280:(4258): 1081–6.
2269:
2263:
2262:
2234:
2228:
2227:
2199:
2193:
2192:
2182:
2172:
2140:
2134:
2133:
2097:
2091:
2090:
2080:
2056:
2050:
2049:
2039:
2016:The EMBO Journal
2007:
2001:
1997:
1991:
1990:
1954:
1948:
1947:
1927:
1921:
1920:
1900:
1894:
1893:
1857:
1851:
1850:
1832:
1782:Scaffold protein
1747:Immunoglobulin E
1727:clonal selection
1716:multiple myeloma
1681:Alfred G. Gilman
1636:'s discovery of
1541:calcium channels
1450:MAPK/ERK pathway
1399:(EGF) binds the
1341:hydrogen sulfide
1277:protein kinase C
1263:Lipid messengers
1232:named after the
1048:nuclear membrane
1010:dendritic spines
1008:remodelling the
895:epithelial cells
806:small G proteins
748:insulin receptor
599:adaptor proteins
392:osmotic pressure
358:mechanosensation
234:steroid hormones
200:. These include
93:first messengers
21:
6350:
6349:
6345:
6344:
6343:
6341:
6340:
6339:
6310:
6309:
6308:
6296:
6288:
6286:
6281:
6213:
6179:
6142:
6121:
6117:Lipid signaling
6089:
6061:
6008:
5933:
5924:
5894:
5889:
5877:
5826:
5805:
5780:
5764:
5736:
5703:
5694:Arginine kinase
5682:
5639:
5598:
5391:
5387:Phospholipase C
5370:
5340:
5261:
5243:
5173:
5140:
5126:
5041:
5036:G alpha subunit
5027:
4983:
4915:
4889:
4870:
4865:
4811:Wayback Machine
4795:Wayback Machine
4777:Wayback Machine
4763:Wayback Machine
4750:Wayback Machine
4704:Wayback Machine
4693:
4688:
4683:
4679:
4674:
4670:
4665:
4661:
4648:
4644:
4638:
4634:
4629:
4625:
4619:
4615:
4610:
4606:
4601:
4597:
4592:
4588:
4582:
4578:
4573:
4569:
4564:
4560:
4555:
4551:
4545:
4541:
4536:
4532:
4525:
4511:
4507:
4462:
4458:
4419:
4415:
4370:
4366:
4335:
4331:
4312:
4308:
4271:(5751): 17–22.
4261:
4254:
4249:
4245:
4206:
4202:
4157:
4153:
4148:
4141:
4134:
4116:
4109:
4074:Nature Medicine
4070:
4066:
4021:
4017:
3978:
3974:
3951:(12): 2811–20.
3937:
3933:
3894:
3887:
3850:
3846:
3815:
3811:
3779:
3775:
3768:
3754:
3747:
3716:
3712:
3675:(6913): 324–9.
3665:
3661:
3632:(11): 1144–50.
3622:
3618:
3579:(5633): 640–3.
3565:
3561:
3506:
3502:
3457:
3450:
3405:
3401:
3370:
3366:
3335:
3328:
3281:
3277:
3246:
3242:
3211:
3207:
3160:
3156:
3125:
3121:
3090:(20): 6241–51.
3076:
3069:
3024:
3020:
2973:
2969:
2962:
2946:
2942:
2897:
2893:
2854:
2845:
2837:
2833:
2832:
2828:
2799:Pflügers Archiv
2791:
2787:
2750:
2746:
2699:
2695:
2658:Current Biology
2650:
2643:
2598:
2594:
2557:
2553:
2516:
2509:
2462:
2458:
2413:
2409:
2370:
2366:
2327:(7418): 61–70.
2313:
2309:
2270:
2266:
2235:
2231:
2200:
2196:
2141:
2137:
2098:
2094:
2065:Current Biology
2057:
2053:
2022:(16): 4338–48.
2008:
2004:
1998:
1994:
1971:10.1038/nrc3983
1955:
1951:
1944:
1928:
1924:
1917:
1901:
1897:
1874:10.1038/nrm1570
1858:
1854:
1847:
1833:
1829:
1825:
1777:Adaptor protein
1773:
1712:myeloma protein
1704:
1599:William Bayliss
1595:Ernest Starling
1559:
1536:
1530:
1522:
1518:
1509:diacyl glycerol
1497:
1427:
1421:
1394:
1384:
1362:genetic program
1353:
1337:carbon monoxide
1325:redox signaling
1321:
1319:Redox signaling
1285:
1265:
1252:when inactive.
1242:
1221:
1198:
1189:
1183:
1157:that activates
1105:signal sequence
1083:transactivation
1067:gene expression
1024:
1018:
993:
987:
943:
937:
888:differentiation
848:
842:
784:protein kinases
780:protein kinases
768:phosphorylation
760:phosphorylation
756:plasma membrane
729:
645:
639:
624:
607:protein domains
595:
576:tyrosine kinase
559:plasma membrane
551:
535:
491:circadian clock
479:
473:
423:
417:
407:present in the
388:
382:
327:focal adhesions
311:
305:
286:are capable of
277:adrenal medulla
246:promoter region
189:
183:
143:
137:
35:
28:
23:
22:
15:
12:
11:
5:
6348:
6338:
6337:
6335:Neurochemistry
6332:
6330:Cell signaling
6327:
6322:
6307:
6306:
6283:
6282:
6280:
6279:
6274:
6269:
6264:
6259:
6258:
6257:
6247:
6242:
6241:
6240:
6235:
6227:
6221:
6219:
6218:Other concepts
6215:
6214:
6212:
6211:
6206:
6197:
6191:
6189:
6185:
6184:
6181:
6180:
6178:
6177:
6172:
6167:
6162:
6156:
6154:
6148:
6147:
6144:
6143:
6141:
6140:
6135:
6129:
6127:
6123:
6122:
6120:
6119:
6114:
6109:
6103:
6097:
6091:
6090:
6088:
6087:
6082:
6077:
6071:
6069:
6063:
6062:
6060:
6059:
6054:
6052:Growth factors
6049:
6044:
6031:
6025:
6023:
6014:
6010:
6009:
6007:
6006:
6001:
5996:
5991:
5986:
5981:
5976:
5971:
5970:
5969:
5964:
5954:
5949:
5947:
5941:
5939:
5935:
5934:
5927:Cell signaling
5923:
5922:
5915:
5908:
5900:
5891:
5890:
5882:
5879:
5878:
5876:
5875:
5870:
5865:
5860:
5855:
5850:
5845:
5840:
5834:
5832:
5828:
5827:
5825:
5824:
5815:
5813:
5807:
5806:
5804:
5803:
5794:
5792:
5786:
5785:
5782:
5781:
5779:
5778:
5772:
5770:
5766:
5765:
5763:
5762:
5757:
5747:
5745:
5738:
5737:
5735:
5734:
5728:
5726:
5716:
5709:
5708:
5705:
5704:
5702:
5701:
5696:
5690:
5688:
5684:
5683:
5681:
5680:
5679:
5678:
5673:
5668:
5663:
5658:
5647:
5645:
5641:
5640:
5638:
5637:
5632:
5631:
5630:
5625:
5615:
5609:
5607:
5600:
5599:
5597:
5596:
5595:
5594:
5584:
5583:
5582:
5577:
5567:
5566:
5565:
5560:
5555:
5550:
5540:
5539:
5538:
5533:
5523:
5522:
5521:
5516:
5511:
5506:
5496:
5495:
5494:
5489:
5484:
5474:
5473:
5472:
5467:
5462:
5457:
5452:
5442:
5441:
5440:
5430:
5429:
5428:
5423:
5412:
5410:
5400:
5398:protein kinase
5393:
5392:
5390:
5389:
5384:
5378:
5376:
5372:
5371:
5369:
5368:
5363:
5358:
5352:
5350:
5346:
5345:
5342:
5341:
5339:
5338:
5333:
5328:
5323:
5318:
5313:
5308:
5307:
5306:
5301:
5296:
5286:
5281:
5275:
5273:
5267:
5266:
5263:
5262:
5260:
5259:
5254:
5248:
5245:
5244:
5242:
5241:
5240:
5239:
5234:
5229:
5224:
5219:
5214:
5209:
5204:
5199:
5194:
5189:
5184:
5179:
5171:
5168:
5167:
5166:
5161:
5156:
5151:
5146:
5138:
5131:
5128:
5127:
5125:
5124:
5123:
5122:
5117:
5112:
5107:
5102:
5097:
5092:
5087:
5082:
5077:
5072:
5067:
5062:
5057:
5052:
5047:
5039:
5032:
5029:
5028:
5026:
5025:
5020:
5015:
5010:
5005:
5000:
4994:
4992:
4985:
4984:
4982:
4981:
4976:
4971:
4966:
4961:
4960:
4959:
4944:
4942:
4932:
4930:Heterotrimeric
4923:
4917:
4916:
4914:
4913:
4908:
4903:
4897:
4895:
4891:
4890:
4888:
4887:
4878:
4876:
4872:
4871:
4864:
4863:
4856:
4849:
4841:
4835:
4834:
4829:
4820:
4801:
4785:
4780:
4766:
4753:
4740:
4730:
4717:
4711:
4706:
4692:
4691:External links
4689:
4687:
4686:
4677:
4668:
4659:
4642:
4632:
4623:
4613:
4604:
4595:
4586:
4576:
4567:
4558:
4549:
4539:
4530:
4523:
4505:
4476:(4): 1278–84.
4456:
4413:
4364:
4329:
4306:
4252:
4243:
4216:(1): 551–600.
4200:
4151:
4139:
4132:
4107:
4086:10.1038/nm1087
4064:
4015:
3972:
3931:
3885:
3844:
3809:
3773:
3766:
3745:
3710:
3659:
3616:
3559:
3520:(11): 4730–5.
3500:
3471:(2): 1470–84.
3448:
3419:(1): 286–300.
3399:
3374:Cancer Letters
3364:
3326:
3289:Genome Biology
3275:
3240:
3221:(9): 489–505.
3205:
3154:
3119:
3067:
3038:(4): 2017–22.
3018:
2987:(48): 7753–7.
2967:
2960:
2940:
2891:
2864:(5): 1414–25.
2843:
2826:
2785:
2764:(3): 387–401.
2744:
2693:
2641:
2592:
2571:(12): 3056–9.
2551:
2530:(9): 1587–97.
2507:
2456:
2407:
2364:
2307:
2264:
2245:(1): 189–225.
2229:
2210:(1): 189–222.
2194:
2155:(5): 2168–70.
2135:
2092:
2051:
2002:
1992:
1949:
1942:
1922:
1916:978-3527313976
1915:
1895:
1852:
1845:
1826:
1824:
1821:
1820:
1819:
1814:
1809:
1804:
1799:
1794:
1792:Cell signaling
1789:
1784:
1779:
1772:
1769:
1703:
1697:
1661:Martin Rodbell
1630:growth factors
1587:adrenal glands
1575:Claude Bernard
1558:
1555:
1554:
1553:
1534:
1528:
1520:
1516:
1495:
1491:
1477:
1454:growth factors
1420:
1419:Major pathways
1417:
1413:
1412:
1409:
1406:
1405:
1404:
1391:
1352:
1349:
1345:semiconductive
1320:
1317:
1284:
1281:
1269:diacylglycerol
1264:
1261:
1257:cell migration
1240:
1219:
1197:
1194:
1185:Main article:
1182:
1179:
1153:interact with
1020:Main article:
1017:
1014:
989:Main article:
986:
983:
939:Main article:
936:
933:
844:Main article:
841:
838:
728:
725:
709:point mutation
698:phospholipases
653:rhodopsin-like
641:Main article:
638:
635:
622:
593:
550:
547:
534:
531:
475:Main article:
472:
469:
419:Main article:
416:
413:
409:primary cilium
384:Main article:
381:
378:
370:proprioception
307:Main article:
304:
301:
202:growth factors
185:Main article:
182:
179:
139:Main article:
136:
133:
68:of genes, and
26:
9:
6:
4:
3:
2:
6347:
6336:
6333:
6331:
6328:
6326:
6323:
6321:
6318:
6317:
6315:
6305:
6300:
6295:
6294:
6291:
6278:
6275:
6273:
6270:
6268:
6265:
6263:
6260:
6256:
6253:
6252:
6251:
6248:
6246:
6243:
6239:
6236:
6234:
6231:
6230:
6228:
6226:
6223:
6222:
6220:
6216:
6210:
6207:
6205:
6201:
6198:
6196:
6193:
6192:
6190:
6186:
6176:
6173:
6171:
6168:
6166:
6163:
6161:
6158:
6157:
6155:
6153:
6149:
6139:
6136:
6134:
6131:
6130:
6128:
6124:
6118:
6115:
6113:
6110:
6108:
6105:
6104:
6101:
6098:
6096:
6092:
6086:
6083:
6081:
6080:Intracellular
6078:
6076:
6073:
6072:
6070:
6068:
6064:
6058:
6055:
6053:
6050:
6048:
6045:
6043:
6042:Neurohormones
6039:
6038:Neuropeptides
6035:
6032:
6030:
6027:
6026:
6024:
6022:
6018:
6015:
6011:
6005:
6002:
6000:
5997:
5995:
5992:
5990:
5989:Fas apoptosis
5987:
5985:
5982:
5980:
5977:
5975:
5972:
5968:
5965:
5963:
5960:
5959:
5958:
5955:
5953:
5950:
5948:
5946:
5943:
5942:
5940:
5936:
5932:
5928:
5921:
5916:
5914:
5909:
5907:
5902:
5901:
5898:
5888:
5887:
5880:
5874:
5871:
5869:
5866:
5864:
5861:
5859:
5856:
5854:
5851:
5849:
5846:
5844:
5841:
5839:
5836:
5835:
5833:
5829:
5823:
5822:
5817:
5816:
5814:
5812:
5808:
5802:
5801:
5796:
5795:
5793:
5791:
5787:
5777:
5774:
5773:
5771:
5767:
5761:
5758:
5756:
5752:
5749:
5748:
5746:
5743:
5739:
5733:
5730:
5729:
5727:
5724:
5720:
5717:
5715:
5710:
5700:
5697:
5695:
5692:
5691:
5689:
5685:
5677:
5674:
5672:
5669:
5667:
5664:
5662:
5659:
5657:
5654:
5653:
5652:
5649:
5648:
5646:
5642:
5636:
5633:
5629:
5626:
5624:
5621:
5620:
5619:
5616:
5614:
5611:
5610:
5608:
5605:
5601:
5593:
5590:
5589:
5588:
5585:
5581:
5578:
5576:
5573:
5572:
5571:
5568:
5564:
5561:
5559:
5556:
5554:
5551:
5549:
5546:
5545:
5544:
5541:
5537:
5534:
5532:
5529:
5528:
5527:
5524:
5520:
5517:
5515:
5512:
5510:
5507:
5505:
5502:
5501:
5500:
5497:
5493:
5490:
5488:
5485:
5483:
5480:
5479:
5478:
5475:
5471:
5468:
5466:
5463:
5461:
5458:
5456:
5453:
5451:
5448:
5447:
5446:
5443:
5439:
5436:
5435:
5434:
5431:
5427:
5424:
5422:
5419:
5418:
5417:
5416:Casein kinase
5414:
5413:
5411:
5408:
5404:
5401:
5399:
5394:
5388:
5385:
5383:
5380:
5379:
5377:
5373:
5367:
5364:
5362:
5359:
5357:
5354:
5353:
5351:
5347:
5337:
5334:
5332:
5329:
5327:
5324:
5322:
5319:
5317:
5314:
5312:
5309:
5305:
5302:
5300:
5297:
5295:
5292:
5291:
5290:
5287:
5285:
5282:
5280:
5277:
5276:
5274:
5272:
5268:
5258:
5255:
5253:
5250:
5249:
5246:
5238:
5235:
5233:
5230:
5228:
5225:
5223:
5220:
5218:
5215:
5213:
5210:
5208:
5205:
5203:
5200:
5198:
5195:
5193:
5190:
5188:
5185:
5183:
5180:
5178:
5175:
5174:
5169:
5165:
5162:
5160:
5157:
5155:
5152:
5150:
5147:
5145:
5142:
5141:
5136:
5133:
5132:
5129:
5121:
5118:
5116:
5113:
5111:
5108:
5106:
5103:
5101:
5098:
5096:
5093:
5091:
5088:
5086:
5083:
5081:
5078:
5076:
5073:
5071:
5068:
5066:
5063:
5061:
5058:
5056:
5053:
5051:
5048:
5046:
5043:
5042:
5037:
5034:
5033:
5030:
5024:
5021:
5019:
5016:
5014:
5011:
5009:
5006:
5004:
5001:
4999:
4996:
4995:
4993:
4990:
4986:
4980:
4977:
4975:
4972:
4970:
4967:
4965:
4962:
4958:
4954:
4951:
4950:
4949:
4946:
4945:
4943:
4940:
4936:
4933:
4931:
4927:
4924:
4922:
4918:
4912:
4909:
4907:
4904:
4902:
4899:
4898:
4896:
4892:
4886:
4885:
4880:
4879:
4877:
4873:
4869:
4862:
4857:
4855:
4850:
4848:
4843:
4842:
4839:
4833:
4830:
4828:
4824:
4821:
4819:
4816:
4812:
4808:
4805:
4802:
4800:
4796:
4792:
4789:
4786:
4784:
4781:
4778:
4774:
4771:
4767:
4764:
4760:
4757:
4754:
4751:
4747:
4744:
4741:
4738:
4734:
4731:
4728:
4724:
4722:
4718:
4715:
4712:
4710:
4707:
4705:
4701:
4698:
4695:
4694:
4681:
4672:
4663:
4656:
4652:
4646:
4636:
4627:
4617:
4608:
4599:
4590:
4580:
4571:
4562:
4553:
4543:
4534:
4526:
4520:
4516:
4509:
4501:
4497:
4493:
4489:
4484:
4479:
4475:
4471:
4467:
4460:
4452:
4448:
4444:
4440:
4436:
4432:
4428:
4424:
4417:
4409:
4405:
4400:
4395:
4391:
4387:
4383:
4379:
4375:
4368:
4360:
4356:
4352:
4348:
4345:(9): 528–35.
4344:
4340:
4333:
4325:
4321:
4317:
4310:
4302:
4298:
4294:
4290:
4286:
4282:
4278:
4274:
4270:
4266:
4259:
4257:
4247:
4239:
4235:
4231:
4227:
4223:
4219:
4215:
4211:
4204:
4196:
4192:
4187:
4182:
4178:
4174:
4170:
4166:
4162:
4155:
4146:
4144:
4135:
4129:
4124:
4123:
4114:
4112:
4103:
4099:
4095:
4091:
4087:
4083:
4080:(8): 789–99.
4079:
4075:
4068:
4060:
4056:
4051:
4046:
4042:
4038:
4034:
4030:
4026:
4019:
4011:
4007:
4003:
3999:
3995:
3991:
3988:(3): 168–72.
3987:
3983:
3976:
3968:
3964:
3959:
3954:
3950:
3946:
3942:
3935:
3927:
3923:
3919:
3915:
3911:
3907:
3903:
3899:
3892:
3890:
3881:
3877:
3872:
3867:
3863:
3859:
3855:
3848:
3840:
3836:
3832:
3828:
3825:(9): 1237–8.
3824:
3820:
3813:
3805:
3801:
3797:
3793:
3790:(2): 379–90.
3789:
3785:
3777:
3769:
3763:
3759:
3752:
3750:
3741:
3737:
3733:
3729:
3725:
3721:
3714:
3706:
3702:
3698:
3694:
3690:
3686:
3682:
3678:
3674:
3670:
3663:
3655:
3651:
3647:
3643:
3639:
3638:10.1038/ni986
3635:
3631:
3627:
3620:
3612:
3608:
3604:
3600:
3595:
3590:
3586:
3582:
3578:
3574:
3570:
3563:
3555:
3551:
3546:
3541:
3536:
3531:
3527:
3523:
3519:
3515:
3511:
3504:
3496:
3492:
3487:
3482:
3478:
3474:
3470:
3466:
3462:
3455:
3453:
3444:
3440:
3435:
3430:
3426:
3422:
3418:
3414:
3410:
3403:
3395:
3391:
3387:
3383:
3379:
3375:
3368:
3360:
3356:
3352:
3348:
3345:(1): 163–80.
3344:
3340:
3333:
3331:
3322:
3318:
3313:
3308:
3303:
3298:
3294:
3290:
3286:
3279:
3271:
3267:
3263:
3259:
3255:
3251:
3244:
3236:
3232:
3228:
3224:
3220:
3216:
3209:
3201:
3197:
3193:
3189:
3185:
3181:
3177:
3173:
3169:
3165:
3158:
3150:
3146:
3142:
3138:
3135:(11): 443–7.
3134:
3130:
3123:
3115:
3111:
3106:
3101:
3097:
3093:
3089:
3085:
3081:
3074:
3072:
3063:
3059:
3055:
3051:
3046:
3041:
3037:
3033:
3029:
3022:
3014:
3010:
3005:
3000:
2995:
2990:
2986:
2982:
2978:
2971:
2963:
2957:
2953:
2952:
2944:
2936:
2932:
2927:
2922:
2918:
2914:
2911:(10): 740–7.
2910:
2906:
2902:
2895:
2887:
2883:
2879:
2875:
2871:
2867:
2863:
2859:
2852:
2850:
2848:
2836:
2830:
2822:
2818:
2813:
2808:
2805:(5): 849–55.
2804:
2800:
2796:
2789:
2781:
2777:
2772:
2767:
2763:
2759:
2755:
2748:
2740:
2736:
2732:
2728:
2724:
2720:
2716:
2712:
2708:
2704:
2697:
2689:
2685:
2680:
2675:
2671:
2667:
2664:(8): R304-7.
2663:
2659:
2655:
2648:
2646:
2637:
2633:
2628:
2623:
2619:
2615:
2612:(2): 300–72.
2611:
2607:
2603:
2596:
2588:
2584:
2579:
2574:
2570:
2566:
2562:
2555:
2547:
2543:
2538:
2533:
2529:
2525:
2521:
2514:
2512:
2503:
2499:
2495:
2491:
2487:
2483:
2479:
2475:
2471:
2467:
2460:
2452:
2448:
2444:
2440:
2435:
2430:
2427:(7): 811–27.
2426:
2422:
2421:FASEB Journal
2418:
2411:
2403:
2399:
2395:
2391:
2387:
2383:
2379:
2375:
2368:
2360:
2356:
2351:
2346:
2342:
2338:
2334:
2330:
2326:
2322:
2318:
2311:
2303:
2299:
2295:
2291:
2287:
2283:
2279:
2275:
2268:
2260:
2256:
2252:
2248:
2244:
2240:
2233:
2225:
2221:
2217:
2213:
2209:
2205:
2198:
2190:
2186:
2181:
2176:
2171:
2166:
2162:
2158:
2154:
2150:
2146:
2139:
2131:
2127:
2123:
2119:
2115:
2111:
2108:(4): 240–51.
2107:
2103:
2096:
2088:
2084:
2079:
2074:
2071:(7): R236-9.
2070:
2066:
2062:
2055:
2047:
2043:
2038:
2033:
2029:
2025:
2021:
2017:
2013:
2006:
1996:
1988:
1984:
1980:
1976:
1972:
1968:
1965:(9): 515–27.
1964:
1960:
1953:
1945:
1939:
1935:
1934:
1926:
1918:
1912:
1908:
1907:
1899:
1891:
1887:
1883:
1879:
1875:
1871:
1868:(2): 99–111.
1867:
1863:
1856:
1848:
1846:9780123741455
1842:
1838:
1831:
1827:
1818:
1815:
1813:
1810:
1808:
1805:
1803:
1800:
1798:
1795:
1793:
1790:
1788:
1785:
1783:
1780:
1778:
1775:
1774:
1768:
1764:
1761:
1755:
1752:
1748:
1744:
1739:
1737:
1732:
1728:
1723:
1721:
1717:
1713:
1708:
1702:
1696:
1694:
1693:review papers
1690:
1686:
1682:
1678:
1674:
1670:
1666:
1662:
1657:
1655:
1651:
1647:
1643:
1639:
1635:
1631:
1627:
1626:Stanley Cohen
1623:
1620:in 1954, and
1619:
1615:
1610:
1608:
1604:
1600:
1596:
1592:
1588:
1584:
1580:
1576:
1568:
1563:
1550:
1546:
1542:
1539:, particular
1538:
1526:
1514:
1510:
1506:
1503:
1499:
1492:
1489:
1485:
1481:
1478:
1475:
1471:
1470:cell division
1467:
1463:
1459:
1455:
1451:
1448:
1447:
1446:
1439:
1431:
1426:
1416:
1410:
1407:
1402:
1398:
1395:For example,
1392:
1389:
1382:
1381:
1379:
1378:
1377:
1374:
1370:
1369:growth factor
1365:
1363:
1359:
1348:
1346:
1342:
1338:
1334:
1330:
1326:
1316:
1314:
1311:, and penile
1310:
1306:
1302:
1298:
1294:
1290:
1280:
1278:
1274:
1270:
1260:
1258:
1253:
1251:
1246:
1238:
1235:
1231:
1227:
1223:
1215:
1211:
1207:
1203:
1193:
1188:
1178:
1176:
1175:interleukin-1
1172:
1168:
1164:
1160:
1156:
1152:
1148:
1144:
1140:
1135:
1133:
1132:prostaglandin
1129:
1125:
1121:
1117:
1115:
1111:
1106:
1102:
1098:
1094:
1090:
1086:
1084:
1080:
1075:
1070:
1068:
1064:
1060:
1055:
1053:
1049:
1045:
1041:
1037:
1033:
1029:
1023:
1013:
1011:
1005:
1003:
999:
992:
982:
980:
976:
972:
968:
964:
960:
956:
952:
948:
942:
932:
930:
926:
922:
921:
914:
912:
908:
904:
900:
896:
891:
889:
885:
884:proliferation
881:
877:
873:
869:
865:
857:
852:
847:
837:
834:
830:
828:
824:
820:
816:
811:
807:
803:
799:
794:
793:
789:
788:pseudokinases
785:
781:
777:
773:
769:
765:
761:
757:
753:
749:
745:
744:growth factor
741:
737:
733:
724:
722:
718:
714:
710:
705:
703:
699:
693:
691:
687:
684:
683:
682:Dictyostelium
678:
674:
670:
666:
662:
658:
657:secretin-like
654:
650:
644:
634:
632:
628:
620:
616:
612:
608:
603:
600:
596:
589:
585:
581:
577:
573:
568:
565:
560:
556:
546:
544:
543:extracellular
540:
539:intracellular
530:
528:
524:
520:
516:
512:
508:
504:
500:
496:
492:
488:
484:
478:
468:
466:
462:
458:
455:
451:
447:
443:
440:
436:
432:
428:
422:
421:Thermoception
412:
410:
406:
401:
397:
393:
387:
377:
375:
371:
367:
363:
359:
355:
351:
347:
343:
339:
336:
332:
328:
324:
320:
316:
310:
300:
298:
294:
289:
285:
280:
278:
274:
270:
266:
262:
261:neuropeptides
258:
254:
249:
247:
243:
239:
235:
231:
227:
223:
219:
215:
211:
207:
203:
199:
195:
188:
178:
176:
172:
168:
164:
161:
157:
147:
142:
128:
124:
122:
118:
114:
110:
106:
102:
98:
94:
90:
85:
83:
79:
75:
71:
67:
63:
62:transcription
57:
55:
51:
47:
43:
39:
33:
19:
6325:Cell biology
6277:Gap junction
6112:Ca signaling
6075:Cell surface
5930:
5883:
5818:
5797:
5433:eIF-2 kinase
4881:
4756:LitInspector
4726:
4720:
4714:TRANSPATH(R)
4680:
4671:
4662:
4645:
4635:
4626:
4616:
4607:
4598:
4589:
4579:
4570:
4561:
4552:
4542:
4533:
4514:
4508:
4473:
4469:
4459:
4429:(1): 69–77.
4426:
4422:
4416:
4384:(3): 701–7.
4381:
4377:
4367:
4342:
4338:
4332:
4315:
4309:
4268:
4264:
4246:
4213:
4209:
4203:
4171:(6): 490–6.
4168:
4165:EMBO Reports
4164:
4154:
4121:
4077:
4073:
4067:
4032:
4028:
4018:
3985:
3981:
3975:
3948:
3945:FEBS Letters
3944:
3934:
3901:
3897:
3861:
3857:
3847:
3822:
3818:
3812:
3787:
3783:
3776:
3757:
3723:
3719:
3713:
3672:
3668:
3662:
3629:
3625:
3619:
3576:
3572:
3562:
3517:
3513:
3503:
3468:
3464:
3416:
3412:
3402:
3377:
3373:
3367:
3342:
3338:
3292:
3288:
3278:
3253:
3249:
3243:
3218:
3214:
3208:
3167:
3163:
3157:
3132:
3128:
3122:
3087:
3084:Biochemistry
3083:
3035:
3031:
3021:
2984:
2980:
2970:
2951:Biochemistry
2950:
2943:
2908:
2904:
2894:
2861:
2857:
2829:
2802:
2798:
2788:
2761:
2757:
2747:
2706:
2702:
2696:
2661:
2657:
2609:
2605:
2595:
2568:
2564:
2554:
2527:
2523:
2469:
2465:
2459:
2424:
2420:
2410:
2377:
2373:
2367:
2324:
2320:
2310:
2277:
2273:
2267:
2242:
2238:
2232:
2207:
2203:
2197:
2152:
2148:
2138:
2105:
2101:
2095:
2068:
2064:
2054:
2019:
2015:
2005:
1995:
1962:
1958:
1952:
1932:
1925:
1905:
1898:
1865:
1861:
1855:
1836:
1830:
1787:Biosemiotics
1765:
1756:
1740:
1724:
1709:
1705:
1688:
1684:
1658:
1611:
1572:
1502:phospholipid
1498:/DAG pathway
1444:
1414:
1366:
1354:
1322:
1289:free radical
1286:
1283:Nitric oxide
1266:
1254:
1250:calreticulin
1214:mitochondria
1199:
1190:
1136:
1118:
1087:
1079:dimerization
1074:zinc fingers
1071:
1056:
1044:progesterone
1040:testosterone
1025:
1006:
994:
944:
924:
918:
915:
892:
861:
855:
831:
795:
730:
706:
702:ion channels
694:
680:
646:
604:
580:phosphatases
569:
564:conformation
552:
536:
519:photopigment
481:In mammals,
480:
456:
424:
398:between the
389:
386:Osmoreceptor
338:cytoskeleton
312:
287:
281:
250:
193:
190:
152:
108:
100:
96:
92:
86:
58:
37:
36:
6188:By distance
6126:Assistants:
6085:Co-receptor
5120:GNA15/GNA16
4906:Calcineurin
3726:(1): 10–6.
3380:(1): 1–25.
3256:(1): 1–11.
1527:. IP
1358:neutrophils
1297:NO synthase
1155:RIP2 kinase
868:fibronectin
719:due to the
613:domains of
567:cytoplasm.
545:receptors.
461:prokaryotes
415:Temperature
319:Eumetazoans
269:epinephrine
218:fibronectin
160:replicative
91:are termed
74:cell growth
66:translation
6314:Categories
6255:Pheromones
6195:Juxtacrine
5526:Lim kinase
5477:IκB kinase
4998:Transducin
2000:35:1902-22
1823:References
1701:Immunology
1638:cyclic AMP
1511:(DAG) and
1329:superoxide
1143:eukaryotic
911:thrombosis
899:leukocytes
823:expression
776:metabolism
721:expression
673:smoothened
615:calmodulin
588:cyclic AMP
572:eukaryotic
523:melanopsin
515:cone cells
465:eukaryotes
396:osmolarity
380:Osmolarity
323:attachment
265:endorphins
222:hyaluronan
78:metabolism
6209:Endocrine
6204:Paracrine
6200:Autocrine
6067:Receptors
6047:Cytokines
5884:see also
5790:Apoptosis
5271:Monomeric
5003:Gustducin
4921:G protein
4640:2285-2291
4102:205383514
2402:205225137
1743:basophils
1673:G-protein
1659:In 1970,
1650:paracrine
1646:autocrine
1537:receptors
1462:receptors
1373:apoptosis
1313:erections
1309:apoptosis
1237:ryanodine
1222:-receptor
1204:into the
1171:cytokines
1124:precursor
1114:crosstalk
1093:chaperone
1050:into the
1038:hormones
979:induction
907:platelets
880:apoptosis
840:Integrins
827:oncogenes
810:isoprenyl
713:chemokine
649:G protein
533:Receptors
507:rhodopsin
354:selectins
350:cadherins
226:integrins
206:cytokines
46:receptors
6029:Hormones
5979:JAK-STAT
5967:MAPK/ERK
5962:TGF beta
5742:Tyrosine
5687:Arginine
5604:Tyrosine
4817:PATHWAY
4807:Archived
4791:Archived
4773:Archived
4759:Archived
4746:Archived
4721:Science'
4700:Archived
4500:29355685
4451:62775788
4230:11283321
4195:15940278
4094:15286780
4059:16293107
4010:25515586
4002:10707088
3967:16678165
3839:19735727
3804:25422863
3740:17126540
3705:16163262
3697:12447441
3654:13016860
3646:14556004
3611:19276476
3603:12855817
3554:17360592
3495:27208244
3443:21398259
3394:16725254
3359:17084981
3321:12372152
3270:15158434
3235:24818526
3200:26554314
3192:12471243
3114:16700535
3062:45743458
3054:10438939
3013:17203515
2935:21873996
2878:15687224
2821:17351786
2780:16269358
2731:16554823
2688:23618661
2636:12040128
2587:18003769
2546:21852585
2494:16079835
2451:21267494
2443:16675838
2394:21654799
2359:23000897
2224:11826268
2189:12606724
2130:20654561
2102:Steroids
2087:16581495
2046:12169636
1987:35252401
1979:26289315
1882:15654321
1771:See also
1665:glucagon
1603:secretin
1591:hormones
1460:surface
1293:arginine
1273:ceramide
1234:alkaloid
1212:and the
1167:caspases
1063:promoter
872:collagen
846:Integrin
817:such as
764:tyrosine
669:frizzled
665:adhesion
586:such as
489:and the
348:such as
331:integrin
263:such as
257:dopamine
253:odorants
216:such as
163:telomere
117:analysis
6304:Biology
6160:General
5984:Akt/PKB
5868:EDARADD
5853:Mucin-4
5592:RPS6KA1
5438:EIF2AK3
4894:Calcium
4727:Science
4621:345-353
4547:211-250
4399:1172772
4324:4621276
4301:5650340
4293:6101906
4273:Bibcode
4238:6747529
4186:1369102
4050:1316260
3926:2442814
3906:Bibcode
3898:Science
3880:8021233
3677:Bibcode
3581:Bibcode
3573:Science
3545:1838668
3522:Bibcode
3486:4902592
3434:3091050
3172:Bibcode
3164:Science
3149:3075366
3105:4301406
3004:4087537
2926:3177959
2886:7938806
2739:4311262
2711:Bibcode
2679:3685181
2502:4374012
2474:Bibcode
2350:3465532
2329:Bibcode
2282:Bibcode
2274:Science
2259:9457173
2157:Bibcode
2122:8733009
1933:Biology
1890:3065483
1607:insulin
1583:thyroid
1567:MEDLINE
1557:History
1549:calcium
1543:in the
1525:cytosol
1466:protein
1206:cytosol
1196:Calcium
1128:retinol
1052:nucleus
1036:steroid
998:synapse
858:(2007).
754:in the
740:ligands
611:EF hand
497:in the
400:cytosol
374:balance
362:hearing
333:-bound
181:Ligands
135:Stimuli
121:disease
89:Ligands
6290:Portal
6013:Agents
5873:PRKCSH
5712:Other
5661:DYRK1B
5656:DYRK1A
5396:Other
5366:Cyclin
5349:Cyclin
4739:(MeSH)
4521:
4498:
4492:376714
4490:
4449:
4443:857951
4441:
4408:782447
4406:
4396:
4359:169771
4357:
4322:
4299:
4291:
4265:Nature
4236:
4228:
4193:
4183:
4130:
4100:
4092:
4057:
4047:
4008:
4000:
3965:
3924:
3878:
3837:
3802:
3764:
3738:
3703:
3695:
3669:Nature
3652:
3644:
3609:
3601:
3552:
3542:
3493:
3483:
3441:
3431:
3392:
3357:
3319:
3312:244915
3309:
3268:
3233:
3198:
3190:
3147:
3112:
3102:
3060:
3052:
3011:
3001:
2958:
2933:
2923:
2884:
2876:
2819:
2778:
2758:Neuron
2737:
2729:
2703:Nature
2686:
2676:
2634:
2627:120784
2624:
2585:
2544:
2500:
2492:
2466:Nature
2449:
2441:
2400:
2392:
2374:Nature
2357:
2347:
2321:Nature
2302:959823
2300:
2257:
2222:
2187:
2180:151311
2177:
2128:
2120:
2085:
2044:
2037:126171
2034:
1985:
1977:
1940:
1913:
1888:
1880:
1843:
1760:DeLisi
1751:ligand
1731:B cell
1581:, the
1579:spleen
1474:cancer
1390:(PTM))
1339:, and
1305:stroke
1110:serine
973:, and
957:, and
886:, and
856:et al.
792:kinome
752:dimers
736:kinase
503:retina
297:cancer
171:neuron
167:senses
115:, the
6175:TFIIH
6170:TFIID
5994:Hippo
5974:Notch
5831:Other
5769:both:
5676:DYRK4
5671:DYRK3
5666:DYRK2
5628:PTK2B
5613:ZAP70
5580:ROCK2
5575:ROCK1
5536:LIMK2
5531:LIMK1
5519:IRAK4
5514:IRAK3
5509:IRAK2
5504:IRAK1
5492:IKBKG
5470:GSK3B
5465:GSK3A
5460:GSK-3
5375:Lipid
5326:Rhebs
5237:BSCL2
5232:GNG13
5227:GNG12
5222:GNG11
5217:GNG10
5182:GNGT2
5177:GNGT1
5115:GNA14
5110:GNA13
5105:GNA12
5100:GNA11
5075:GNAT3
5070:GNAT2
5065:GNAT1
5060:GNAI3
5055:GNAI2
5050:GNAI1
5045:GNAO1
4496:S2CID
4447:S2CID
4297:S2CID
4234:S2CID
4098:S2CID
4006:S2CID
3701:S2CID
3650:S2CID
3607:S2CID
3196:S2CID
3058:S2CID
2882:S2CID
2838:(PDF)
2735:S2CID
2498:S2CID
2447:S2CID
2398:S2CID
2126:S2CID
1983:S2CID
1886:S2CID
1679:with
1593:" by
1173:like
1163:NALP3
1159:NF-κB
1126:like
967:IRAK4
963:IRAK1
951:TIRAP
947:Myd88
621:. PIP
487:sight
483:light
471:Light
454:ncRNA
450:Hsp90
446:Hsp70
442:Hsp40
366:touch
335:actin
293:EGFRs
5945:GPCR
5819:see
5798:see
5699:McsB
5623:PTK2
5563:PAK4
5558:PAK3
5553:PAK2
5548:PAK1
5487:IKK2
5482:CHUK
5455:GSK2
5450:GSK1
5336:RGKs
5331:Raps
5316:Arfs
5311:Rhos
5304:NRAS
5299:KRAS
5294:HRAS
5284:Rabs
5279:ARFs
5212:GNG8
5207:GNG7
5202:GNG5
5197:GNG4
5192:GNG3
5187:GNG2
5164:GNB5
5159:GNB4
5154:GNB3
5149:GNB2
5144:GNB1
5095:GNAQ
5090:GNAL
5085:GNAS
5080:GNAZ
5013:cGMP
4989:cGMP
4969:cAMP
4939:cAMP
4882:see
4815:KEGG
4519:ISBN
4488:PMID
4439:PMID
4404:PMID
4355:PMID
4320:PMID
4289:PMID
4226:PMID
4191:PMID
4128:ISBN
4090:PMID
4055:PMID
3998:PMID
3963:PMID
3922:PMID
3876:PMID
3835:PMID
3800:PMID
3762:ISBN
3736:PMID
3693:PMID
3642:PMID
3599:PMID
3550:PMID
3491:PMID
3439:PMID
3390:PMID
3355:PMID
3343:1775
3317:PMID
3266:PMID
3231:PMID
3188:PMID
3145:PMID
3110:PMID
3050:PMID
3009:PMID
2956:ISBN
2931:PMID
2874:PMID
2817:PMID
2776:PMID
2727:PMID
2684:PMID
2632:PMID
2583:PMID
2542:PMID
2490:PMID
2439:PMID
2390:PMID
2355:PMID
2298:PMID
2255:PMID
2220:PMID
2185:PMID
2118:PMID
2083:PMID
2042:PMID
1975:PMID
1938:ISBN
1911:ISBN
1878:PMID
1841:ISBN
1687:and
1648:and
1585:and
1458:cell
1271:and
1218:InsP
1151:NOD2
1101:fold
1042:and
1030:and
975:IKKi
971:TBK1
959:TRAM
955:TRIF
929:HAK5
925:ILK1
870:and
819:SOS1
786:and
774:and
700:and
688:and
667:and
590:and
578:and
541:and
513:and
463:and
457:hsr1
448:and
435:HSF1
372:and
352:and
342:YAP1
284:HER2
230:CD44
228:and
220:and
208:and
5957:RTK
5952:Wnt
5635:BTK
5321:Ran
5289:Ras
4875:MAP
4827:NCI
4651:doi
4478:doi
4474:122
4431:doi
4394:PMC
4386:doi
4382:154
4347:doi
4343:101
4281:doi
4269:284
4218:doi
4181:PMC
4173:doi
4082:doi
4045:PMC
4037:doi
4033:392
3990:doi
3953:doi
3949:580
3914:doi
3902:237
3866:doi
3862:269
3827:doi
3792:doi
3788:466
3728:doi
3685:doi
3673:420
3634:doi
3589:doi
3577:301
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