795:
74:
4092:
848:
963:
393:
919:
1076:
707:
695:
384:(such as SOS) recognizes the phosphorylated tyrosine on the receptor. This protein functions as a bridge which connects the RTK to an intermediate protein (such as GNRP), starting the intracellular signaling cascade. In turn, the intermediate protein stimulates GDP-bound Ras to the activated GTP-bound Ras. GAP eventually returns Ras to its inactive state. Activation of
1015:
proliferation. Current research is focused on the action of the Wnt signaling pathway the regulation of stem cell choice to proliferate and self renew. This action of Wnt signaling in the possible control and maintenance of stem cells, may provide a possible treatment in cancers exhibiting aberrant Wnt signaling.
421:(formation of cells in blood). The Kit receptor and related tyrosine kinase receptors actually are inhibitory and effectively suppresses receptor firing. Mutant forms of the Kit receptor, which fire constitutively in a ligand-independent fashion, are found in a diverse array of cancerous malignancies.
437:
transcription is upregulated when Ras is in the GTP-bound state. The chemokines are then released from the cell, free to bind to another nearby cell. Paracrine signaling between neighboring cells creates this positive feedback loop. Thus, the constitutive transcription of upregulated proteins form
1014:
The Wnt signaling pathways are complex, involving many different elements, and therefore have many targets for misregulation. Mutations that cause constitutive activation of the Wnt signaling pathway lead to tumor formation and cancer. Aberrant activation of the Wnt pathway can lead to increase cell
2248:
Zsebo, Krisztina M.; Williams, David A.; Geissler, Edwin N.; Broudy, Virginia C.; Martin, Francis H.; Atkins, Harry L.; Hsu, Rou-Yin; Birkett, Neal C.; Okino, Kenneth H.; Murdock, Douglas C.; Jacobsen, Frederick W.; Langley, Keith E.; Smith, Kent A.; Takeish, Takashi; Cattanach, Bruce M.; Galli,
131:
Although the FGF family of paracrine factors has a broad range of functions, major findings support the idea that they primarily stimulate proliferation and differentiation. To fulfill many diverse functions, FGFs can be alternatively spliced or even have different initiation codons to create
1262:
Non-Smad signaling proteins contribute to the responses of the TGF-β pathway in three ways. First, non-Smad signaling pathways phosphorylate the Smads. Second, Smads directly signal to other pathways by communicating directly with other signaling proteins, such as kinases. Finally, the TGF-β
830:
orientation, cell polarity, cadherin mediated adhesion, and early development of embryos in many different organisms. Current research has indicated that deregulation of Wnt signaling plays a role in tumor formation, because at a cellular level, Wnt proteins often regulated
1071:
kinase activity. When a TGF-β superfamily ligand binds to the type II receptor, it recruits a type I receptor and activates it by phosphorylating the serine or threonine residues of its "GS" box. This forms an activation complex that can then phosphorylate SMAD proteins.
2335:
Melillo, Rosa Marina; Castellone, Maria
Domenica; Guarino, Valentina; De Falco, Valentina; Cirafici, Anna Maria; Salvatore, Giuliana; Caiazzo, Fiorina; Basolo, Fulvio; Giannini, Riccardo; Kruhoffer, Mogens; Orntoft, Torben; Fusco, Alfredo; Santoro, Massimo (2005).
621:. Paracrine signaling through the JAK-STAT pathway is necessary in the transition from stationary epithelial cells to mobile mesenchymal cells, which are capable of invading surrounding tissue. Only the JAK-STAT pathway has been found to induce migratory cells.
2650:
Shiang, Rita; Thompson, Leslie M.; Zhu, Ya-Zhen; Church, Deanna M.; Fielder, Thomas J.; Bocian, Maureen; Winokur, Sara T.; Wasmuth, John J. (1994). "Mutations in the transmembrane domain of FGFR3 cause the most common genetic form of dwarfism, achondroplasia".
1002:
The Wnt signaling pathways are critical in cell-cell signaling during normal development and embryogenesis and required for maintenance of adult tissue, therefore it is not difficult to understand why disruption in Wnt signaling pathways can promote human
579:
The JAK-STAT signaling pathway is instrumental in the development of limbs, specifically in its ability to regulate bone growth through paracrine signaling of cytokines. However, mutations in this pathway have been implicated in severe forms of dwarfism:
388:
has the potential to initiate three signaling pathways downstream of Ras: Ras→Raf→MAP kinase pathway, PI3 kinase pathway, and Ral pathway. Each pathway leads to the activation of transcription factors which enter the nucleus to alter gene expression.
2614:
Bonaventure, J.; Rousseau, F.; Legeai-Mallet, L.; Le Merrer, M.; Munnich, A.; Maroteaux, P. (1996). "Common mutations in the fibroblast growth factor receptor 3 (FGFR3) gene account for achondroplasia, hypochondroplasia, and thanatophoric dwarfism".
1063:. There are five kinds of type II receptors and seven types of type I receptors in humans and other mammals. These receptors are known as "dual-specificity kinases" because their cytoplasmic kinase domain has weak tyrosine kinase activity but strong
89:
in the body - even between different species - are known to utilize a similar sets of paracrine factors in differential development. The highly conserved receptors and pathways can be organized into four major families based on similar structures:
954:. Active RhoA is able to induce cytoskeleton changes by activating Roh-associated kinase (ROCK) and affect gene transcription directly. Active Rac can directly induce cytoskeleton changes and affect gene transcription through activation of JNK.
778:. This connection between the Hedgehog signaling pathway and human cancers may provide for the possible of therapeutic intervention as treatment for such cancers. The Hedgehog signaling pathway is also involved in normal regulation of
883:, which is already working on DNA as a repressor, inhibiting the transcription of the genes it binds. Binding of β-catenin to Lef/Tcf works as a transcription activator, activating the transcription of the Wnt-responsive genes.
489:
After dimerization of the cytokine receptors following ligand binding, the JAKs transphosphorylate each other. The resulting phosphotyrosines attract STAT proteins. The STAT proteins dimerize and enter the nucleus to act as
734:(Ci), Fused, and Cos protein complex attached to microtubules to remain intact. In this conformation, the Ci protein is cleaved so that a portion of the protein is allowed to enter the nucleus and act as a transcriptional
368:
receptor. This conformational change activates the dormant kinase of each RTK on the tyrosine residue. Due to the fact that the receptor spans across the membrane from the extracellular environment, through the
1031:, secreted polypeptides that regulate development. Many developmental processes are under its control including gastrulation, axis symmetry of the body, organ morphogenesis, and tissue homeostasis in adults. All
600:
cell division is prematurely terminated, resulting in lethal dwarfism. Rib and limb bone growth plate cells are not transcribed. Thus, the inability of the rib cage to expand prevents the newborn's breathing.
118:
In order for paracrine factors to successfully induce a response in the receiving cell, that cell must have the appropriate receptors available on the cell membrane to receive the signals, also known as being
3481:
Neth, Peter; Ries, Christian; Karow, Marisa; Egea, Virginia; Ilmer, Matthias; Jochum, Marianne (2007). "The Wnt Signal
Transduction Pathway in Stem Cells and Cancer Cells: Influence on Cellular Invasion".
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of the
Hedgehog protein, which would be ligand dependent. In addition, therapy-induced Hedgehog pathway activation has been shown to be necessary for progression of Prostate Cancer tumors after
70:
environment. Factors then travel to nearby cells in which the gradient of factor received determines the outcome. However, the exact distance that paracrine factors can travel is not certain.
633:
is involved in induction of cell types and the creation of tissue boundaries and patterning and are found in all bilateral organisms. Hedgehog proteins were first discovered and studied in
3736:
Wu, Jia-Wei; Hu, Min; Chai, Jijie; Seoane, Joan; Huse, Morgan; Li, Carey; Rigotti, Daniel J.; Kyin, Saw; Muir, Tom W.; Fairman, Robert; Massagué, Joan; Shi, Yigong (2001).
4106:
Betts, J Gordon; Desaix, Peter; Johnson, Eddie; Johnson, Jody E; Korol, Oksana; Kruse, Dean; Poe, Brandon; Wise, James; Womble, Mark D; Young, Kelly A (July 24, 2023).
1844:
is a paracrine that is released by immune cells in the bronchial tree. Histamine causes the smooth muscle cells of the bronchi to constrict, narrowing the airways.
879:
degradation. Thus inhibited GSK3, allows β-catenin to dissociate from APC, accumulate, and travel to nucleus. In the nucleus β-catenin associates with Lef/Tcf
938:. Once again Wnt proteins binds to and activates Frizzled so that Frizzled activates a Dishevelled protein that is tethered to the plasma membrane through a
826:, and the noncanonical Wnt/Ca pathway. Wnt proteins appear to control a wide range of developmental processes and have been seen as necessary for control of
754:
The
Hedgehog Signaling pathway is critical in proper tissue patterning and orientation during normal development of most animals. Hedgehog proteins induce
2249:
Stephen J.; Suggs, Sidney V. (1990). "Stem cell factor is encoded at the SI locus of the mouse and is the ligand for the c-kit tyrosine kinase receptor".
154:
10 are two of the critical players in limb development. In the forelimb initiation and limb growth in mice, axial (lengthwise) cues from the intermediate
1925:
Gospodarowicz, D.; Ferrara, N.; Schweigerer, L.; Neufeld, G. (1987). "Structural
Characterization and Biological Functions of Fibroblast Growth Factor".
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and Slimb, so that the Ci protein is not cleaved. This intact Ci protein can enter the nucleus, associate with CPB protein and act as a transcriptional
438:
ideal environments for tumors to arise. Effectively, multiple bindings of ligands to the RTK receptors overstimulates the Ras-Raf-MAPK pathway, which
81:
Although paracrine signaling elicits a diverse array of responses in the induced cells, most paracrine factors utilize a relatively streamlined set of
462:. Instead of carrying covalently associated tyrosine kinase domains, Jak-STAT receptors form noncovalent complexes with tyrosine kinases of the Jak (
1812:
are paracrine signaling agents. The local action of growth factor signaling plays an especially important role in the development of tissues. Also,
1398:
regulate mature ligand stability and processing, including degrading ligands in lysosomes. BMPs act by diffusing from the cells that create them.
4176:
2628:
1462:
663:) has various roles in vertebrae development, mediating signaling and regulating the organization of central nervous system, limb, and
2394:
1183:
family, which function as transcription factors. Specifically, the type I receptor, activated by the type II receptor, phosphorylates
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in particular. This uncontrolled activation of the
Hedgehog proteins can be caused by mutations to the signal pathway, which would be
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in certain cells and differentiations in others. Aberrant activation of the
Hedgehog pathway has been implicated in several types of
974:
levels. Again Wnt binds and activates to
Frizzled. In this case however activated Frizzled causes a coupled G-protein to activate a
4096:
3875:
Schmierer, Bernhard; Hill, Caroline S. (2007). "TGFβ–SMAD signal transduction: Molecular specificity and functional flexibility".
3002:"Paracrine Sonic Hedgehog Signaling Contributes Significantly to Acquired Steroidogenesis in the Prostate Tumor Microenvironment"
609:
Research on paracrine signaling through the JAK-STAT pathway revealed its potential in activating invasive behavior of ovarian
494:
to alter gene expression. In particular, the STATs transcribe genes that aid in cell proliferation and survival – such as myc.
139:
One of the most important functions of the FGF receptors (FGFR) is in limb development. This signaling involves nine different
1327:. TGF-β proteins regulate epithelia by controlling where and when they branch to form kidney, lung, and salivary gland ducts.
4115:
3679:
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377:, the binding of the receptor to the ligand also causes the trans phosphorylation of the cytoplasmic domain of the receptor.
1820:, functions in a paracrine fashion to regulate gene expression during embryonic development in higher animals. In insects,
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populations, and required for normal growth and regeneration of damaged organs. This may provide another possible route for
417:
encodes a tyrosine kinase receptor whose ligand is a paracrine protein called stem cell factor (SCF), which is important in
4148:
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through phosphorylation. However, when a BMP ligand binds to the receptors, the phosphorylated receptor complex activates
360:. This dimerizes the transmembrane receptor to another RTK receptor, which causes the autophosphorylation and subsequent
4423:
39:
produces a signal to induce changes in nearby cells, altering the behaviour of those cells. Signaling molecules known as
2749:"Paracrine Signaling through the JAK/STAT Pathway Activates Invasive Behavior of Ovarian Epithelial Cells in Drosophila"
738:. In the presence of Hedgehog, Patched no longer inhibits Smoothened. Then active Smoothened protein is able to inhibit
4391:
3000:
Lubik AA, Nouri M, Truong S, Ghaffari M, Adomat HH, Corey E, Cox ME, Li N, Guns ES, Yenki P, Pham S, Buttyan R (2016).
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4169:
1512:
2338:"The RET/PTC-RAS-BRAF linear signaling cascade mediates the motile and mitogenic phenotype of thyroid cancer cells"
730:. In the absence of Hedgehog, the Patched receptor inhibits Smoothened action. Inhibition of Smoothened causes the
32:
1754:
1215:
698:
Production of the CiR transcriptional repressor when Hh is not bound to
Patched. In the diagram, "P" represents
103:
3530:
Bandyopadhyay, Amitabha; Tsuji, Kunikazu; Cox, Karen; Harfe, Brian D.; Rosen, Vicki; Tabin, Clifford J. (2006).
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protein. In its active state the
Dishevelled protein inhibits the activity of the glycogen synthase kinase 3 (
413:. In fact, mutant forms of a single RTK may play a causal role in very different types of cancer. The Kit
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4418:
4162:
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Itoh, Fumiko; Asao, Hironobu; Sugamura, Kazuo; Heldin, Carl-Henrik; Ten Dijke, Peter; Itoh, Susumu (2001).
775:
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Fantl, Wendy J; Johnson, Daniel E; Williams, Lewis T (1993). "Signaling by Receptor Tyrosine Kinases".
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When Hh is bound to Patched (PTCH), Ci protein is able to act as a transcription factor in the nucleus.
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459:
95:
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have been found in vertebrates: sonic hedgehog, desert hedgehog, and Indian hedgehog. Sonic hedgehog (
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455:
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935:
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3051:"A Genetic Screen in Drosophila for Identifying Novel Components of the Hedgehog Signaling Pathway"
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1305:
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209:. These cells are in contact with the outer ectoderm cells, which will eventually become the lens.
91:
3638:
891:
The noncanonical Wnt pathways provide a signal transduction pathway for Wnt that does not involve
794:
4353:
4325:
4252:
4232:
2431:"Meaningful relationships: The regulation of the Ras/Raf/MEK/ERK pathway by protein interactions"
581:
433:
has elucidated the theory that paracrine signaling may aid in creating tumor microenvironments.
82:
3828:"Promoting bone morphogenetic protein signaling through negative regulation of inhibitory Smads"
3393:
Logan, Catriona Y.; Nusse, Roel (2004). "The Wnt Signaling Pathway in Development and Disease".
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defective IL-12-driven Th1 differentiation, increased susceptibility to intracellular pathogens
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4338:
4133:
3402:
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Taipale, Jussi; Beachy, Philip A. (2001). "The Hedgehog and Wnt signaling pathways in cancer".
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206:
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Xu, J.; Xu, J; Colvin, JS; McEwen, DG; MacArthur, CA; Coulier, F; Gao, G; Goldfarb, M (1996).
1871:– either a paracrine hormone, or a hormone acting in both a paracrine and an endocrine fashion
123:. Additionally, the responding cell must also have the ability to be mechanistically induced.
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Munir, Sadia; Xu, Guoxiong; Wu, Yaojiong; Yang, Burton; Lala, Peeyush K.; Peng, Chun (2004).
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Attisano, Liliana; Wrana, Jeffrey L. (2002). "Signal Transduction by the TGF-β Superfamily".
3532:"Genetic Analysis of the Roles of BMP2, BMP4, and BMP7 in Limb Patterning and Skeletogenesis"
3438:
Lustig, B; Behrens, J (2003). "The Wnt signaling pathway and its role in tumor development".
3416:
2481:
Aaronson, David S.; Horvath, Curt M. (2002). "A Road Map for Those Who Don't Know JAK-STAT".
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Katz, Michael E; McCormick, Frank (1997). "Signal transduction from multiple Ras effectors".
1243:
991:
491:
361:
140:
99:
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1027:" (Transforming Growth Factor) is a family of proteins that includes 33 members that encode
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Pavletich, Nikola P.; Hata, Yigong; Lo, Akiko; Massagué, Roger S.; Pavletich, Joan (1997).
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1471:
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1004:
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Additionally, paracrine signaling of Fgf is essential in the developing eye of chicks. The
59:
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Specific TGF-β ligands will result in the activation of either the SMAD2/3 or the SMAD1/5
348:
and activates the RTK pathway. This pathway begins at the cell membrane surface, where a
8:
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2839:
Genes Are Coexpressed at Many Diverse Sites of Cell–Cell Interaction in the Mouse Embryo"
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107:
63:
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2020:
Lappi, Douglas A. (1995). "Tumor targeting through fibroblast growth factor receptors".
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ligands bind to either Type I or Type II receptors, to create heterotetramic complexes.
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Paracrine signaling of growth factors between nearby cells has been shown to exacerbate
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1994:
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is crucial for kidney development, sperm synthesis, and neural tube polarization. Both
1339:, as their name suggests. However, BMPs are very multifunctional and can also regulate
907:
832:
755:
120:
55:
4002:"Nodal and ALK7 Inhibit Proliferation and Induce Apoptosis in Human Trophoblast Cells"
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Rönnstrand, L. (2004). "Signal transduction via the stem cell factor receptor/c-Kit".
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regulates many cellular processes in developing embryo and adult organisms, including
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to release intracellular calcium stores, to induce calcium-dependent gene expression.
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1999:
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Figure of the three main pathways of Wnt signaling in biological signal transduction.
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Wrana, Jeffrey L.; Ozdamar, Barish; Le Roy, Christine; Benchabane, Hassina (2008).
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Nybakken, K; Perrimon, N (2002). "Hedgehog signal transduction: Recent findings".
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3674:. Proteins and Cell Regulation. Vol. 5. Dordrecht: Springer. pp. 1–13.
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over a relatively short distance (local action), as opposed to cell signaling by
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Yarden, Yosef; Ullrich, Axel (1988). "Growth Factor Receptor Tyrosine Kinases".
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3779:"A structural basis for mutational inactivation of the tumour suppressor Smad4"
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Smad Signal Transduction: Smads in Proliferation, Differentiation and Disease
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1355:. They also specify the anterior/posterior axis, induce growth, and regulate
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871:) enzyme. Normally active GSK3 prevents the dissociation of β-catenin to the
811:
783:
715:
686:) is expressed in the gut and cartilage, important in postnatal bone growth.
683:
652:
648:
418:
385:
370:
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Ohkawara, Bisei; Iemura, Shun-Ichiro; Ten Dijke, Peter; Ueno, Naoto (2002).
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10.1002/(SICI)1096-8628(19960503)63:1<148::AID-AJMG26>3.0.CO;2-N
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and either up-regulate or down-regulate in the expression of a target gene.
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1962:"Recent developments in the cell biology of basic fibroblast growth factor"
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1422:
1288:, and TGF-β5. They are involved in positively and negatively regulation of
903:
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family of proteins. The binding of Wnt to a Frizzled protein activates the
675:
639:. Hedgehog proteins produce key signals for the establishment of limb and
463:
283:
3812:
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3217:
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2400:. If this is an intentional citation to a retracted paper, please replace
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2085:
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2003:
1946:
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Phenotype and survival of mice after knockout of some JAK or STAT genes:
396:
Diagram showing key components of a signal transduction pathway. See the
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3961:"Action Range of BMP is Defined by Its N-Terminal Basic Amino Acid Core"
1977:
1938:
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promotes bone formation, causes cell death, or signals the formation of
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1985:
1238:. Then, the Smad2/3 or the Smad1/5 complexes form a dimer complex with
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66:. Cells that produce paracrine factors secrete them into the immediate
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and transmembrane Stbm protein. The active Dishevelled activates RhoA
913:
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2711:
2532:
Rawlings, Jason S.; Rosler, Kristin M.; Harrison, Douglas A. (2004).
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In mature organisms, paracrine signaling is involved in responses to
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1323:. Ultimately, it increases the production of extracellular matrix by
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699:
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106:. Binding of a paracrine factor to its respective receptor initiates
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3339:
3337:
3335:
2790:"Hedgehog signaling in animal development: Paradigms and principles"
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1637:
300:
Development of multiple organs (including limbs, thymus, pituitary)
4305:
2575:"Cytokine signaling in 2002: new surprises in the Jak/Stat pathway"
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binds to its specific receptor. Ligands that bind to RTKs include
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4043:"Retinoic acid synthesis and signaling during early organogenesis"
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706:
443:
356:, epidermal growth factors, platelet-derived growth factors, and
51:
43:
4110:. Houston: OpenStax CNX. 17.1 Overview of the endocrine system.
3632:
3630:
3628:
2334:
1824:
controls growth through paracrine action on the corpora allata.
333:
pathway. This signaling pathway has been highly studied, using
113:
1727:
1723:
1718:
1675:
1671:
1633:
1628:
1599:
1594:
1562:
1557:
1539:
1504:
1500:
1494:
1247:
1203:
1184:
1162:
1124:
1103:
1093:
1064:
1008:
943:
767:
664:
574:
349:
345:
202:
1882:– A curated resource of signal transduction pathways in humans
1330:
694:
3625:
2876:
2874:
2573:
O'Shea, John J; Gadina, Massimo; Schreiber, Robert D (2002).
2060:"Receptor Specificity of the Fibroblast Growth Factor Family"
1788:
1784:
1779:
1774:
1770:
1742:
1737:
1733:
1693:
1688:
1684:
1681:
1666:
1652:
1647:
1643:
1623:
1614:
1609:
1605:
1577:
1572:
1568:
1363:
1211:
896:
593:
592:
gene, causing a premature and constitutive activation of the
3636:
3958:
2926:"New players and puzzles in the Hedgehog signaling pathway"
2247:
1833:
1589:
1518:
1395:
1391:
1387:
1379:
1375:
1371:
868:
714:
Members of the Hedgehog protein family act by binding to a
198:
3529:
3290:
Chen, Xi; Yang, Jun; Evans, Paul M; Liu, Chunming (2008).
2871:
1335:
Members of the BMP family were originally found to induce
886:
859:, Wnt proteins binds to its transmembrane receptor of the
4105:
3097:
2881:
Jacob, L.; Lum, L. (2007). "Hedgehog Signaling Pathway".
2572:
320:
201:
becomes localized in what differentiates into the neural
4184:
3525:
3523:
3521:
2999:
970:
The noncanonical Wnt/Ca pathway regulates intracellular
749:
215:
and survival of mice after knockout of some FGFR genes:
126:
3776:
2649:
3825:
2531:
842:
746:, inducing the expression of Hedgehog-response genes.
3518:
3192:"Wnt signaling: A common theme in animal development"
3098:
Evangelista, M.; Tian, H.; De Sauvage, F. J. (2006).
2101:"Finger or toe: The molecular basis of limb identity"
1401:
818:
cascades via three different pathways, the canonical
2142:
1263:
receptors directly phosphorylate non-Smad proteins.
1250:
involved in the pathway, there is only one co-SMAD,
997:
957:
3670:. In ten Dijke, Peter; Heldin, Carl-Henrik (eds.).
3231:
3229:
3227:
914:
The noncanonical planar cell polarity (PCP) pathway
329:and its respective receptors utilizes the receptor
54:which travel considerably longer distances via the
3918:Moustakas, Aristidis; Heldin, Carl-Henrik (2005).
3238:"Signal transduction by the Wnt family of ligands"
588:dwarfism (viable). This is due to a mutation in a
3480:
2696:"The basics of epithelial-mesenchymal transition"
4548:
3440:Journal of Cancer Research and Clinical Oncology
3289:
3224:
2964:
2057:
1959:
895:. In the noncanonical pathways, Wnt affects the
486:(important for mediating immune cell function).
3917:
3665:
3395:Annual Review of Cell and Developmental Biology
3285:
3283:
3281:
2693:
2480:
1266:
1179:The TGF-β superfamily activates members of the
726:" protein, by which the Hedgehog signal can be
3735:
3666:ten Dijke, Peter; Heldin, Carl-Henrik (2006).
2828:
922:Noncanonical Wnt Planar Cell Polarity pathway.
604:
4170:
3999:
3874:
3738:"Crystal Structure of a Phosphorylated Smad2"
3580:
3437:
3138:
2967:Current Opinion in Genetics & Development
2930:Current Opinion in Genetics & Development
2829:Bitgood, Mark J.; McMahon, Andrew P. (1995).
2787:
2742:
2215:Current Opinion in Genetics & Development
2212:
2177:
1960:Rifkin, Daniel B.; Moscatelli, David (1989).
689:
114:Paracrine factors induce competent responders
3819:
3729:
3278:
3189:
3048:
2924:Johnson, Ronald L; Scott, Matthew P (1998).
2923:
2694:Kalluri, Raghu; Weinberg, Robert A. (2009).
2607:
1918:
946:through Dishevelled associated activator of
926:The noncanonical PCP pathway regulates cell
575:Aberrant JAK-STAT pathway and bone mutations
3770:
3641:. In Derynck, Rik; Miyazono, Kohei (eds.).
3343:
2476:
2474:
1386:, depending on the tissue it is acting on.
1364:bone morphogenetic protein receptor type II
1331:2. Bone morphogenetic protein (BMPs) family
255:Inner ear, skeletal (tail) differentiation
182:8, which also stimulates the production of
4177:
4163:
3392:
3100:"The Hedgehog Signaling Pathway in Cancer"
2414:|...|intentional=yes}}
2291:
2285:
1195:and enters the nucleus, where they act as
1191:. The R-SMAD/Co-SMAD forms a complex with
978:(PLC), which interacts with and splits PIP
404:
286:defect, CNS development, limb development
162:5, which subsequently signals to the same
4136:at the U.S. National Library of Medicine
4066:
4017:
3976:
3935:
3851:
3802:
3753:
3712:
3694:
3639:"Signaling Receptors of the TGF-β Family"
3557:
3547:
3406:
3369:
3315:
3261:
3207:
3115:
3074:
3017:
2941:
2854:
2805:
2764:
2719:
2590:
2549:
2454:
2361:
2116:
2075:
1993:
1513:Growth and differentiation factors (GDFs)
1079:SMAD Signaling Pathway Activated by TGF-β
424:
110:cascades, eliciting different responses.
77:Overview of signal transduction pathways.
3417:10.1146/annurev.cellbio.20.010403.113126
2880:
2525:
2471:
2138:
2136:
2053:
2051:
1519:Summary table of TGF-β signaling pathway
1463:Glial-Derived Neurotrophic Factor (GDNF)
1074:
961:
917:
846:
793:
705:
693:
391:
72:
4040:
4034:
2687:
2643:
2328:
2015:
2013:
1483:Involved in mammalian sex determination
887:The noncanonical Wnt signaling pathways
770:independent, or a mutation that causes
655:. At least three "Drosophila" hedgehog
4549:
2736:
2566:
2171:
466:) class. These receptors bind are for
321:Receptor tyrosine kinase (RTK) pathway
4158:
3877:Nature Reviews Molecular Cell Biology
3344:Komiya, Yuko; Habas, Raymond (2008).
3292:"Wnt signaling: The good and the bad"
2428:
2422:
2241:
2133:
2098:
2048:
2019:
1953:
1366:(BMPR2). Some of the proteins of the
750:Hedgehog signaling pathway and cancer
127:Fibroblast growth factor (FGF) family
3296:Acta Biochimica et Biophysica Sinica
3235:
2617:American Journal of Medical Genetics
2294:Cellular and Molecular Life Sciences
2206:
2092:
2010:
1319:and inhibits the degradation of the
1018:
4424:Transcription preinitiation complex
3695:Moustakas, Aristidis (2002-09-01).
2788:Ingham, P. W.; McMahon, AP (2001).
2192:10.1146/annurev.bi.57.070188.002303
2157:10.1146/annurev.bi.62.070193.002321
1311:TGF-β1 stimulates the synthesis of
1257:
990:can then bind to a receptor on the
843:The canonical Wnt signaling pathway
722:" receptor, which is bound to the "
647:of adult tissues, involved in late
449:
13:
4392:Signal transducing adaptor protein
3346:"Wnt signal transduction pathways"
3190:Cadigan, K. M.; Nusse, R. (1997).
3049:Collins, R. T.; Cohen, SM (2005).
1832:, tissue repair, the formation of
1402:Other members of TGF-β superfamily
1271:
1088:There are three classes of SMADs:
851:Canonical Wnt pathway without Wnt.
824:planar cell polarity (PCP) pathway
806:family includes a large number of
624:
14:
4568:
4127:
4041:Duester, Gregg (September 2008).
2700:Journal of Clinical Investigation
2342:Journal of Clinical Investigation
1110:Examples of SMADs in each class:
998:Wnt signaling pathways and cancer
966:Noncanonical Wnt/calcium pathway.
85:and pathways. In fact, different
4095: This article incorporates
4090:
3308:10.1111/j.1745-7270.2008.00440.x
2534:"The JAK/STAT signaling pathway"
1038:
617:transition is highly evident in
446:and invasive capacity of cells.
16:Form of localized cell signaling
4006:Journal of Biological Chemistry
3993:
3952:
3911:
3868:
3688:
3659:
3645:. CSHL Press. pp. 151–77.
3574:
3474:
3431:
3386:
3183:
3132:
3091:
3042:
3006:International Journal of Cancer
2993:
2958:
2917:
2822:
2781:
2064:Journal of Biological Chemistry
1187:that then bind to the co-SMAD,
1083:
958:The noncanonical Wnt/Ca pathway
1897:
1222:receptor complex can activate
1099:Common-mediator SMAD (Co-SMAD)
269:Inner cell mass proliferation
1:
3978:10.1016/S0960-9822(01)00684-4
3755:10.1016/S1097-2765(01)00421-X
3117:10.1158/1078-0432.CCR-06-1736
2979:10.1016/S0959-437X(02)00333-7
2943:10.1016/S0959-437X(98)80117-2
2766:10.1016/S0092-8674(01)00607-9
2592:10.1016/S0092-8674(02)00701-8
2227:10.1016/S0959-437X(97)80112-8
2180:Annual Review of Biochemistry
2145:Annual Review of Biochemistry
1891:
789:
190:10 results in limbless mice.
4149:Dorland's Medical Dictionary
3549:10.1371/journal.pgen.0020216
2665:10.1016/0092-8674(94)90302-6
2263:10.1016/0092-8674(90)90302-U
1499:Forms receptor complex with
1267:Members of TGF-β superfamily
1218:binds to the receptors, the
814:. The Wnt proteins activate
776:androgen deprivation therapy
454:In addition to RTK pathway,
325:Paracrine signaling through
7:
3067:10.1534/genetics.104.039420
1966:The Journal of Cell Biology
1847:
1800:
1662:Bone morphogenetic proteins
1526:TGF Beta superfamily ligand
1479:Müllerian Inhibitory Factor
1442:Nerve cell survival factors
605:JAK-STAT pathway and cancer
557:Tissue specific phenotypes
10:
4573:
4059:10.1016/j.cell.2008.09.002
2022:Seminars in Cancer Biology
1505:Activin A Type 1C receptor
1501:Activin A Type 1B receptor
1495:Activin A Type 2B receptor
875:protein, which results in
786:via the Hedgehog pathway.
690:Hedgehog signaling pathway
643:of fruit flies as well as
531:Failure in erythropoiesis
460:JAK-STAT signaling pathway
132:hundreds of different FGF
4476:
4446:
4409:
4384:
4361:
4352:
4324:
4278:
4271:
4196:
3496:10.1007/s12015-007-0001-y
3452:10.1007/s00432-003-0431-0
2447:10.1042/0264-6021:3510289
2306:10.1007/s00018-004-4189-6
1092:Receptor-regulated SMAD (
456:fibroblast growth factors
354:fibroblast growth factors
327:fibroblast growth factors
4504:Neuroendocrine signaling
4138:Medical Subject Headings
4108:Anatomy & Physiology
3920:"Non-Smad TGF-β signals"
3844:10.1093/emboj/20.15.4132
3697:"Smad signaling network"
3236:Dale, Trevor C. (1998).
3104:Clinical Cancer Research
2077:10.1074/jbc.271.25.15292
1246:. Though there are many
835:, cell morphology, cell
337:eyes and human cancers.
92:fibroblast growth factor
3924:Journal of Cell Science
3714:10.1242/jcs.115.17.3355
3701:Journal of Cell Science
3603:10.1126/science.1071809
3242:The Biochemical Journal
3196:Genes & Development
2895:10.1126/stke.4072007cm6
2794:Genes & Development
2538:Journal of Cell Science
2503:10.1126/science.1071545
2435:The Biochemical Journal
1292:, the formation of the
631:Hedgehog protein family
582:thanatophoric dysplasia
405:RTK receptor and cancer
340:Binding of FGF to FGFR
314:Cerebellar Development
178:to begin production of
174:10 then signals to the
60:juxtacrine interactions
4366:cAMP-dependent pathway
4019:10.1074/jbc.M400641200
3209:10.1101/gad.11.24.3286
2856:10.1006/dbio.1995.0010
2429:Kolch, Walter (2000).
2034:10.1006/scbi.1995.0036
1875:MAPK signaling pathway
1854:cAMP dependent pathway
1467:Needed for kidney and
1306:TGF-β type II receptor
1080:
967:
923:
852:
799:
711:
703:
674:) is expressed in the
596:transcription factor.
458:can also activate the
425:RTK pathway and cancer
401:
78:
33:cellular communication
4492:Synaptic transmission
4488:Neurocrine signaling
4411:Transcription factors
4258:PI3K/AKT/mTOR pathway
2843:Developmental Biology
2406:|...}}
2377:(Retracted, see
1816:, the active form of
1362:The BMPs bind to the
1276:This family includes
1244:transcription factors
1206:. For instance, when
1197:transcription factors
1078:
992:endoplasmic reticulum
965:
921:
850:
797:
709:
697:
613:. This epithelial to
492:transcription factors
395:
362:conformational change
141:alternatively spliced
76:
4099:available under the
3362:10.4161/org.4.2.5851
1321:extracellular matrix
1294:extracellular matrix
1005:degenerative disease
881:transcription factor
764:Basal Cell Carcinoma
520:Neurologic Deficits
400:article for details.
4557:Signal transduction
4521:Mechanotransduction
4509:Exocrine signalling
4316:Signaling molecules
4190:Signal transduction
4134:Paracrine+Signaling
3795:1997Natur.388R..87S
3595:2002Sci...296.1646A
3153:2001Natur.411..349T
2495:2002Sci...296.1653A
1978:10.1083/jcb.109.1.1
1939:10.1210/edrv-8-2-95
1905:"Paracrine Factors"
1886:Paracrine regulator
1859:Crosstalk (biology)
822:, the noncanonical
816:signal transduction
732:Cubitus interruptus
682:. Indian hedgehog (
670:. Desert hedgehog (
542:Human dwarfism and
108:signal transduction
64:autocrine signaling
25:paracrine signaling
4531:Ion channel gating
4263:Integrin receptors
4197:Signaling pathways
2807:10.1101/gad.938601
2745:Montell, Denise J.
2743:Silver, Debra L.;
2300:(19–20): 2535–48.
2099:Logan, M. (2003).
1547:Ligand Inhibitors
1081:
968:
924:
908:gene transcription
853:
833:cell proliferation
800:
756:cell proliferation
712:
704:
402:
221:FGFR Knockout Gene
79:
56:circulatory system
4544:
4543:
4526:Phototransduction
4484:Intracrine action
4442:
4441:
4405:
4404:
4293:Neurotransmitters
4117:978-1-947172-04-3
3937:10.1242/jcs.02554
3681:978-1-4020-4709-1
3668:"The Smad family"
3652:978-0-87969-752-5
3484:Stem Cell Reviews
3254:10.1042/bj3290209
3019:10.1002/ijc.30450
2551:10.1242/jcs.00963
2118:10.1242/dev.00956
1927:Endocrine Reviews
1798:
1797:
1177:
1176:
1102:Inhibitory SMAD (
1019:TGF-β superfamily
857:canonical pathway
839:, and cell fate.
572:
571:
318:
317:
186:10. Deletion of
146:of the receptor.
104:TGF-β superfamily
48:endocrine factors
41:paracrine factors
4564:
4497:Chemical synapse
4397:Scaffold protein
4359:
4358:
4354:Second messenger
4280:Receptor ligands
4276:
4275:
4179:
4172:
4165:
4156:
4155:
4122:
4121:
4094:
4087:
4081:
4080:
4070:
4038:
4032:
4031:
4021:
4012:(30): 31277–86.
3997:
3991:
3990:
3980:
3956:
3950:
3949:
3939:
3915:
3909:
3908:
3872:
3866:
3865:
3855:
3832:The EMBO Journal
3823:
3817:
3816:
3806:
3774:
3768:
3767:
3757:
3733:
3727:
3726:
3716:
3692:
3686:
3685:
3663:
3657:
3656:
3643:The TGF-β Family
3634:
3623:
3622:
3589:(5573): 1646–7.
3578:
3572:
3571:
3561:
3551:
3527:
3516:
3515:
3478:
3472:
3471:
3435:
3429:
3428:
3410:
3390:
3384:
3383:
3373:
3341:
3330:
3329:
3319:
3287:
3276:
3275:
3265:
3248:(Pt 2): 209–23.
3233:
3222:
3221:
3211:
3202:(24): 3286–305.
3187:
3181:
3180:
3161:10.1038/35077219
3147:(6835): 349–54.
3136:
3130:
3129:
3119:
3095:
3089:
3088:
3078:
3046:
3040:
3039:
3021:
2997:
2991:
2990:
2962:
2956:
2955:
2945:
2921:
2915:
2914:
2878:
2869:
2868:
2858:
2826:
2820:
2819:
2809:
2785:
2779:
2778:
2768:
2740:
2734:
2733:
2723:
2712:10.1172/JCI39104
2691:
2685:
2684:
2647:
2641:
2640:
2611:
2605:
2604:
2594:
2570:
2564:
2563:
2553:
2529:
2523:
2522:
2489:(5573): 1653–5.
2478:
2469:
2468:
2458:
2426:
2420:
2419:
2417:
2415:
2407:
2396:Retraction Watch
2383:10.1172/JCI87345
2375:
2365:
2354:10.1172/JCI22758
2332:
2326:
2325:
2289:
2283:
2282:
2245:
2239:
2238:
2210:
2204:
2203:
2175:
2169:
2168:
2140:
2131:
2130:
2120:
2096:
2090:
2089:
2079:
2055:
2046:
2045:
2017:
2008:
2007:
1997:
1957:
1951:
1950:
1922:
1916:
1915:
1913:
1911:
1901:
1810:clotting factors
1530:Type II Receptor
1523:
1522:
1325:epithelial cells
1258:Non-SMAD pathway
1113:
1112:
950:(Daam1) and the
611:epithelial cells
544:craniosynostosis
500:
499:
482:formation), and
450:JAK-STAT pathway
398:MAPK/ERK pathway
358:stem cell factor
218:
217:
21:cellular biology
4572:
4571:
4567:
4566:
4565:
4563:
4562:
4561:
4547:
4546:
4545:
4540:
4472:
4438:
4401:
4380:
4376:Lipid signaling
4348:
4320:
4267:
4192:
4183:
4130:
4125:
4118:
4088:
4084:
4039:
4035:
3998:
3994:
3965:Current Biology
3957:
3953:
3930:(16): 3573–84.
3916:
3912:
3889:10.1038/nrm2297
3873:
3869:
3838:(15): 4132–42.
3824:
3820:
3789:(6637): 87–93.
3775:
3771:
3734:
3730:
3693:
3689:
3682:
3664:
3660:
3653:
3635:
3626:
3579:
3575:
3528:
3519:
3479:
3475:
3436:
3432:
3391:
3387:
3342:
3333:
3288:
3279:
3234:
3225:
3188:
3184:
3137:
3133:
3096:
3092:
3047:
3043:
2998:
2994:
2963:
2959:
2922:
2918:
2879:
2872:
2827:
2823:
2800:(23): 3059–87.
2786:
2782:
2741:
2737:
2692:
2688:
2648:
2644:
2612:
2608:
2571:
2567:
2530:
2526:
2479:
2472:
2427:
2423:
2409:
2401:
2399:
2376:
2333:
2329:
2290:
2286:
2246:
2242:
2211:
2207:
2176:
2172:
2141:
2134:
2111:(26): 6401–10.
2097:
2093:
2070:(25): 15292–7.
2056:
2049:
2018:
2011:
1958:
1954:
1923:
1919:
1909:
1907:
1903:
1902:
1898:
1894:
1864:Lipid signaling
1850:
1827:
1803:
1535:Type I Receptor
1521:
1472:differentiation
1435:, gonadal, and
1404:
1353:differentiation
1333:
1304:. They bind to
1296:between cells,
1274:
1272:1. TGF-β family
1269:
1260:
1086:
1053:differentiation
1041:
1021:
1000:
989:
985:
982:into DAG and IP
981:
960:
948:morphogenesis 1
940:Prickle protein
916:
889:
845:
792:
752:
692:
680:spermatogenesis
627:
625:Hedgehog family
607:
577:
478:(important for
470:(important for
452:
427:
407:
382:adaptor protein
373:, and into the
323:
129:
116:
17:
12:
11:
5:
4570:
4560:
4559:
4542:
4541:
4539:
4538:
4533:
4528:
4523:
4518:
4517:
4516:
4506:
4501:
4500:
4499:
4494:
4486:
4480:
4478:
4477:Other concepts
4474:
4473:
4471:
4470:
4465:
4456:
4450:
4448:
4444:
4443:
4440:
4439:
4437:
4436:
4431:
4426:
4421:
4415:
4413:
4407:
4406:
4403:
4402:
4400:
4399:
4394:
4388:
4386:
4382:
4381:
4379:
4378:
4373:
4368:
4362:
4356:
4350:
4349:
4347:
4346:
4341:
4336:
4330:
4328:
4322:
4321:
4319:
4318:
4313:
4311:Growth factors
4308:
4303:
4290:
4284:
4282:
4273:
4269:
4268:
4266:
4265:
4260:
4255:
4250:
4245:
4240:
4235:
4230:
4229:
4228:
4223:
4213:
4208:
4206:
4200:
4198:
4194:
4193:
4186:Cell signaling
4182:
4181:
4174:
4167:
4159:
4153:
4152:
4141:
4129:
4128:External links
4126:
4124:
4123:
4116:
4082:
4033:
3992:
3951:
3910:
3883:(12): 970–82.
3867:
3818:
3769:
3748:(6): 1277–89.
3742:Molecular Cell
3728:
3707:(17): 3355–6.
3687:
3680:
3658:
3651:
3624:
3573:
3517:
3473:
3446:(4): 199–221.
3430:
3408:10.1.1.322.311
3385:
3331:
3277:
3223:
3182:
3131:
3110:(20): 5924–8.
3090:
3041:
3012:(2): 358–369.
2992:
2957:
2916:
2883:Science's STKE
2870:
2821:
2780:
2735:
2686:
2642:
2606:
2585:(2): S121–31.
2565:
2524:
2470:
2441:(2): 289–305.
2421:
2348:(4): 1068–81.
2327:
2284:
2240:
2205:
2170:
2132:
2091:
2047:
2009:
1952:
1917:
1895:
1893:
1890:
1889:
1888:
1883:
1877:
1872:
1866:
1861:
1856:
1849:
1846:
1802:
1799:
1796:
1795:
1782:
1777:
1768:
1762:
1757:
1751:
1750:
1745:
1740:
1731:
1721:
1716:
1710:
1709:
1696:
1691:
1679:
1669:
1664:
1658:
1657:
1655:
1650:
1641:
1631:
1626:
1620:
1619:
1617:
1612:
1603:
1597:
1592:
1586:
1585:
1580:
1575:
1566:
1560:
1555:
1549:
1548:
1545:
1542:
1537:
1532:
1527:
1520:
1517:
1516:
1515:
1510:
1509:
1508:
1497:
1486:
1485:
1484:
1476:
1475:
1474:
1469:enteric neuron
1460:
1459:
1458:
1443:
1440:
1425:
1413:Activin Family
1410:
1403:
1400:
1345:cell migration
1337:bone formation
1332:
1329:
1273:
1270:
1268:
1265:
1259:
1256:
1220:phosphorylated
1175:
1174:
1165:
1159:
1158:
1153:
1149:
1148:
1127:
1121:
1120:
1117:
1108:
1107:
1100:
1097:
1085:
1082:
1040:
1037:
1020:
1017:
999:
996:
987:
983:
979:
959:
956:
915:
912:
888:
885:
844:
841:
791:
788:
772:overexpression
751:
748:
691:
688:
626:
623:
606:
603:
586:achondroplasic
576:
573:
570:
569:
566:
563:
559:
558:
555:
552:
548:
547:
540:
537:
533:
532:
529:
526:
522:
521:
518:
515:
511:
510:
507:
504:
476:thrombopoietin
472:erythropoiesis
468:erythropoietin
451:
448:
431:thyroid cancer
426:
423:
415:proto-oncogene
411:carcinogenesis
406:
403:
342:phosphorylates
322:
319:
316:
315:
312:
309:
302:
301:
298:
295:
288:
287:
281:
278:
271:
270:
267:
264:
257:
256:
253:
250:
243:
242:
239:
236:
229:
228:
225:
222:
128:
125:
115:
112:
94:(FGF) family,
29:cell signaling
15:
9:
6:
4:
3:
2:
4569:
4558:
4555:
4554:
4552:
4537:
4534:
4532:
4529:
4527:
4524:
4522:
4519:
4515:
4512:
4511:
4510:
4507:
4505:
4502:
4498:
4495:
4493:
4490:
4489:
4487:
4485:
4482:
4481:
4479:
4475:
4469:
4466:
4464:
4460:
4457:
4455:
4452:
4451:
4449:
4445:
4435:
4432:
4430:
4427:
4425:
4422:
4420:
4417:
4416:
4414:
4412:
4408:
4398:
4395:
4393:
4390:
4389:
4387:
4383:
4377:
4374:
4372:
4369:
4367:
4364:
4363:
4360:
4357:
4355:
4351:
4345:
4342:
4340:
4339:Intracellular
4337:
4335:
4332:
4331:
4329:
4327:
4323:
4317:
4314:
4312:
4309:
4307:
4304:
4302:
4301:Neurohormones
4298:
4297:Neuropeptides
4294:
4291:
4289:
4286:
4285:
4283:
4281:
4277:
4274:
4270:
4264:
4261:
4259:
4256:
4254:
4251:
4249:
4248:Fas apoptosis
4246:
4244:
4241:
4239:
4236:
4234:
4231:
4227:
4224:
4222:
4219:
4218:
4217:
4214:
4212:
4209:
4207:
4205:
4202:
4201:
4199:
4195:
4191:
4187:
4180:
4175:
4173:
4168:
4166:
4161:
4160:
4157:
4151:
4150:
4145:
4142:
4139:
4135:
4132:
4131:
4119:
4113:
4109:
4104:
4102:
4098:
4093:
4086:
4078:
4074:
4069:
4064:
4060:
4056:
4053:(6): 921–31.
4052:
4048:
4044:
4037:
4029:
4025:
4020:
4015:
4011:
4007:
4003:
3996:
3988:
3984:
3979:
3974:
3970:
3966:
3962:
3955:
3947:
3943:
3938:
3933:
3929:
3925:
3921:
3914:
3906:
3902:
3898:
3894:
3890:
3886:
3882:
3878:
3871:
3863:
3859:
3854:
3849:
3845:
3841:
3837:
3833:
3829:
3822:
3814:
3810:
3805:
3804:10.1038/40431
3800:
3796:
3792:
3788:
3784:
3780:
3773:
3765:
3761:
3756:
3751:
3747:
3743:
3739:
3732:
3724:
3720:
3715:
3710:
3706:
3702:
3698:
3691:
3683:
3677:
3673:
3669:
3662:
3654:
3648:
3644:
3640:
3633:
3631:
3629:
3620:
3616:
3612:
3608:
3604:
3600:
3596:
3592:
3588:
3584:
3577:
3569:
3565:
3560:
3555:
3550:
3545:
3541:
3537:
3536:PLOS Genetics
3533:
3526:
3524:
3522:
3513:
3509:
3505:
3501:
3497:
3493:
3489:
3485:
3477:
3469:
3465:
3461:
3457:
3453:
3449:
3445:
3441:
3434:
3426:
3422:
3418:
3414:
3409:
3404:
3400:
3396:
3389:
3381:
3377:
3372:
3367:
3363:
3359:
3355:
3351:
3350:Organogenesis
3347:
3340:
3338:
3336:
3327:
3323:
3318:
3313:
3309:
3305:
3302:(7): 577–94.
3301:
3297:
3293:
3286:
3284:
3282:
3273:
3269:
3264:
3259:
3255:
3251:
3247:
3243:
3239:
3232:
3230:
3228:
3219:
3215:
3210:
3205:
3201:
3197:
3193:
3186:
3178:
3174:
3170:
3166:
3162:
3158:
3154:
3150:
3146:
3142:
3135:
3127:
3123:
3118:
3113:
3109:
3105:
3101:
3094:
3086:
3082:
3077:
3072:
3068:
3064:
3061:(1): 173–84.
3060:
3056:
3052:
3045:
3037:
3033:
3029:
3025:
3020:
3015:
3011:
3007:
3003:
2996:
2988:
2984:
2980:
2976:
2973:(5): 503–11.
2972:
2968:
2961:
2953:
2949:
2944:
2939:
2935:
2931:
2927:
2920:
2912:
2908:
2904:
2900:
2896:
2892:
2888:
2884:
2877:
2875:
2866:
2862:
2857:
2852:
2849:(1): 126–38.
2848:
2844:
2840:
2838:
2834:
2825:
2817:
2813:
2808:
2803:
2799:
2795:
2791:
2784:
2776:
2772:
2767:
2762:
2759:(7): 831–41.
2758:
2754:
2750:
2746:
2739:
2731:
2727:
2722:
2717:
2713:
2709:
2706:(6): 1420–8.
2705:
2701:
2697:
2690:
2682:
2678:
2674:
2670:
2666:
2662:
2659:(2): 335–42.
2658:
2654:
2646:
2638:
2634:
2630:
2626:
2623:(1): 148–54.
2622:
2618:
2610:
2602:
2598:
2593:
2588:
2584:
2580:
2576:
2569:
2561:
2557:
2552:
2547:
2544:(8): 1281–3.
2543:
2539:
2535:
2528:
2520:
2516:
2512:
2508:
2504:
2500:
2496:
2492:
2488:
2484:
2477:
2475:
2466:
2462:
2457:
2452:
2448:
2444:
2440:
2436:
2432:
2425:
2413:
2405:
2398:
2397:
2392:
2388:
2384:
2380:
2373:
2369:
2364:
2359:
2355:
2351:
2347:
2343:
2339:
2331:
2323:
2319:
2315:
2311:
2307:
2303:
2299:
2295:
2288:
2280:
2276:
2272:
2268:
2264:
2260:
2257:(1): 213–24.
2256:
2252:
2244:
2236:
2232:
2228:
2224:
2220:
2216:
2209:
2201:
2197:
2193:
2189:
2185:
2181:
2174:
2166:
2162:
2158:
2154:
2150:
2146:
2139:
2137:
2128:
2124:
2119:
2114:
2110:
2106:
2102:
2095:
2087:
2083:
2078:
2073:
2069:
2065:
2061:
2054:
2052:
2043:
2039:
2035:
2031:
2028:(5): 279–88.
2027:
2023:
2016:
2014:
2005:
2001:
1996:
1991:
1987:
1983:
1979:
1975:
1971:
1967:
1963:
1956:
1948:
1944:
1940:
1936:
1933:(2): 95–114.
1932:
1928:
1921:
1906:
1900:
1896:
1887:
1884:
1881:
1878:
1876:
1873:
1870:
1869:Local hormone
1867:
1865:
1862:
1860:
1857:
1855:
1852:
1851:
1845:
1843:
1839:
1835:
1831:
1825:
1823:
1819:
1815:
1814:retinoic acid
1811:
1807:
1806:Growth factor
1794:
1790:
1786:
1783:
1781:
1778:
1776:
1772:
1769:
1766:
1763:
1761:
1758:
1756:
1753:
1752:
1749:
1746:
1744:
1741:
1739:
1735:
1732:
1729:
1725:
1722:
1720:
1717:
1715:
1712:
1711:
1708:
1704:
1700:
1697:
1695:
1692:
1690:
1686:
1683:
1680:
1677:
1673:
1670:
1668:
1665:
1663:
1660:
1659:
1656:
1654:
1651:
1649:
1645:
1642:
1639:
1635:
1632:
1630:
1627:
1625:
1622:
1621:
1618:
1616:
1613:
1611:
1607:
1604:
1601:
1598:
1596:
1593:
1591:
1588:
1587:
1584:
1581:
1579:
1576:
1574:
1570:
1567:
1564:
1561:
1559:
1556:
1554:
1551:
1550:
1546:
1543:
1541:
1538:
1536:
1533:
1531:
1528:
1525:
1524:
1514:
1511:
1506:
1502:
1498:
1496:
1492:
1491:
1490:
1487:
1482:
1481:
1480:
1477:
1473:
1470:
1466:
1465:
1464:
1461:
1456:
1452:
1448:
1444:
1441:
1438:
1434:
1430:
1426:
1424:
1420:
1419:embryogenesis
1416:
1415:
1414:
1411:
1409:
1406:
1405:
1399:
1397:
1393:
1389:
1385:
1381:
1377:
1373:
1369:
1365:
1360:
1358:
1354:
1350:
1349:cell division
1346:
1342:
1338:
1328:
1326:
1322:
1318:
1314:
1309:
1307:
1303:
1302:embryogenesis
1299:
1295:
1291:
1290:cell division
1287:
1283:
1279:
1264:
1255:
1253:
1249:
1245:
1241:
1237:
1233:
1229:
1225:
1221:
1217:
1213:
1209:
1205:
1200:
1198:
1194:
1190:
1186:
1182:
1173:
1169:
1166:
1164:
1161:
1160:
1157:
1154:
1151:
1150:
1147:
1143:
1139:
1135:
1131:
1128:
1126:
1123:
1122:
1118:
1115:
1114:
1111:
1105:
1101:
1098:
1095:
1091:
1090:
1089:
1077:
1073:
1070:
1066:
1062:
1058:
1054:
1050:
1046:
1045:TGF-β pathway
1039:TGF-β pathway
1036:
1034:
1030:
1026:
1016:
1012:
1010:
1006:
995:
993:
977:
976:phospholipase
973:
964:
955:
953:
949:
945:
941:
937:
933:
929:
920:
911:
909:
905:
902:
898:
894:
884:
882:
878:
874:
870:
866:
862:
858:
849:
840:
838:
834:
829:
825:
821:
817:
813:
812:glycoproteins
809:
805:
796:
787:
785:
784:tumorigenesis
781:
777:
773:
769:
765:
761:
757:
747:
745:
741:
737:
733:
729:
725:
721:
717:
716:transmembrane
708:
701:
696:
687:
685:
681:
677:
676:Sertoli cells
673:
669:
666:
662:
658:
654:
653:metamorphosis
650:
649:embryogenesis
646:
642:
638:
637:
632:
622:
620:
616:
612:
602:
599:
595:
591:
587:
584:(lethal) and
583:
567:
564:
561:
560:
556:
553:
550:
549:
545:
541:
538:
535:
534:
530:
527:
524:
523:
519:
516:
513:
512:
508:
505:
503:Knockout Gene
502:
501:
498:
495:
493:
487:
485:
481:
477:
473:
469:
465:
461:
457:
447:
445:
441:
440:overexpresses
436:
432:
422:
420:
419:hematopoiesis
416:
412:
399:
394:
390:
387:
383:
378:
376:
372:
371:lipid bilayer
367:
366:homodimerized
363:
359:
355:
351:
347:
343:
338:
336:
332:
328:
313:
310:
307:
304:
303:
299:
296:
293:
290:
289:
285:
282:
279:
276:
273:
272:
268:
265:
262:
259:
258:
254:
251:
248:
245:
244:
240:
237:
234:
231:
230:
226:
223:
220:
219:
216:
214:
210:
208:
204:
200:
196:
191:
189:
185:
181:
177:
173:
169:
165:
161:
157:
153:
149:
145:
142:
137:
135:
124:
122:
111:
109:
105:
101:
97:
93:
88:
84:
75:
71:
69:
68:extracellular
65:
61:
57:
53:
49:
45:
42:
38:
34:
30:
27:is a form of
26:
22:
4536:Gap junction
4371:Ca signaling
4334:Cell surface
4147:
4107:
4089:
4085:
4050:
4046:
4036:
4009:
4005:
3995:
3971:(3): 205–9.
3968:
3964:
3954:
3927:
3923:
3913:
3880:
3876:
3870:
3835:
3831:
3821:
3786:
3782:
3772:
3745:
3741:
3731:
3704:
3700:
3690:
3671:
3661:
3642:
3586:
3582:
3576:
3542:(12): e216.
3539:
3535:
3490:(1): 18–29.
3487:
3483:
3476:
3443:
3439:
3433:
3398:
3394:
3388:
3356:(2): 68–75.
3353:
3349:
3299:
3295:
3245:
3241:
3199:
3195:
3185:
3144:
3140:
3134:
3107:
3103:
3093:
3058:
3054:
3044:
3009:
3005:
2995:
2970:
2966:
2960:
2936:(4): 450–6.
2933:
2929:
2919:
2889:(407): cm6.
2886:
2882:
2846:
2842:
2836:
2832:
2824:
2797:
2793:
2783:
2756:
2752:
2738:
2703:
2699:
2689:
2656:
2652:
2645:
2620:
2616:
2609:
2582:
2578:
2568:
2541:
2537:
2527:
2486:
2482:
2438:
2434:
2424:
2410:{{
2402:{{
2395:
2393:,
2345:
2341:
2330:
2297:
2293:
2287:
2254:
2250:
2243:
2218:
2214:
2208:
2183:
2179:
2173:
2148:
2144:
2108:
2104:
2094:
2067:
2063:
2025:
2021:
1969:
1965:
1955:
1930:
1926:
1920:
1908:. Retrieved
1899:
1836:, and blood
1826:
1822:Allatostatin
1804:
1445:3 Activins:
1437:hypothalamic
1423:osteogenesis
1417:Involved in
1361:
1334:
1310:
1275:
1261:
1216:TGF-β ligand
1201:
1178:
1109:
1087:
1084:SMAD pathway
1042:
1022:
1013:
1001:
969:
925:
904:cytoskeleton
901:microtubular
890:
854:
801:
753:
713:
678:involved in
634:
628:
608:
578:
496:
488:
464:Janus kinase
453:
429:Research on
428:
408:
379:
339:
334:
324:
305:
291:
284:Gastrulation
274:
260:
246:
232:
211:
194:
192:
187:
183:
179:
171:
167:
159:
151:
147:
138:
130:
117:
102:family, and
80:
40:
31:, a type of
24:
18:
4447:By distance
4385:Assistants:
4344:Co-receptor
4144:"paracrine"
3401:: 781–810.
2221:(1): 75–9.
2105:Development
1834:scar tissue
1583:Follistatin
1370:family are
1357:homeostasis
1317:fibronectin
1308:(TGFBRII).
1242:and become
1061:homeostasis
1049:cell growth
952:Rac protein
906:as well as
865:Dishevelled
820:Wnt pathway
804:Wnt protein
645:homeostasis
615:mesenchymal
598:Chondrocyte
166:to produce
35:in which a
4514:Pheromones
4454:Juxtacrine
2186:: 443–78.
2151:: 453–81.
1972:(1): 1–6.
1892:References
1455:Activin AB
1408:Vg1 Family
928:morphology
790:Wnt family
728:transduced
724:Smoothened
636:Drosophila
619:metastasis
546:syndromes
509:Phenotype
484:interferon
335:Drosophila
227:Phenotype
4468:Endocrine
4463:Paracrine
4459:Autocrine
4326:Receptors
4306:Cytokines
4101:CC BY 4.0
3403:CiteSeerX
2412:retracted
2404:retracted
1842:Histamine
1830:allergens
1818:vitamin A
1553:Activin A
1493:Binds to
1451:Activin B
1447:Activin A
1433:pituitary
1427:Regulate
1384:epidermis
1341:apoptosis
1298:apoptosis
1069:threonine
1057:apoptosis
893:β-catenin
877:β-catenin
780:stem-cell
744:activator
736:repressor
700:phosphate
641:body plan
444:mitogenic
435:Chemokine
375:cytoplasm
344:the idle
213:Phenotype
207:optic cup
158:produces
121:competent
83:receptors
4551:Category
4288:Hormones
4238:JAK-STAT
4226:MAPK/ERK
4221:TGF beta
4103:license.
4077:18805086
4028:15150278
3987:11839272
3946:16105881
3897:18000526
3862:11483516
3764:11779503
3723:12154066
3619:84138159
3611:12040180
3568:17194222
3512:25793825
3504:17873378
3468:28959851
3460:12707770
3425:15473860
3380:19279717
3326:18604449
3169:11357142
3126:17062662
3085:15744048
3055:Genetics
3028:27672740
2987:12200154
2911:35653781
2903:17925577
2833:Hedgehog
2816:11731473
2775:11779460
2747:(2001).
2730:19487818
2681:20325070
2601:11983158
2560:15020666
2519:20857536
2511:12040185
2465:11023813
2391:27035814
2372:15761501
2314:15526160
2279:39924379
2127:14660539
1848:See also
1838:clotting
1801:Examples
1726:(ALK4),
1674:(ALK3),
1636:(ALK4),
1503:or with
1439:hormones
1313:collagen
1193:importin
936:movement
932:division
861:Frizzled
837:motility
808:cysteine
668:polarity
657:homologs
506:Survival
480:platelet
331:tyrosine
241:Unclear
224:Survival
176:ectoderm
164:mesoderm
156:mesoderm
144:isoforms
134:isoforms
98:family,
96:Hedgehog
52:hormones
4419:General
4243:Akt/PKB
4068:2632951
3813:9214508
3791:Bibcode
3591:Bibcode
3583:Science
3559:1713256
3371:2634250
3317:2532600
3272:9425102
3263:1219034
3218:9407023
3177:4414768
3149:Bibcode
3076:1449730
3036:2354209
2952:9729722
2865:7589793
2721:2689101
2673:7913883
2637:8723101
2491:Bibcode
2483:Science
2456:1221363
2363:1062891
2322:2602233
2271:1698556
2235:9024640
2200:3052279
2165:7688944
2086:8663044
2042:8562905
2004:2545723
1995:2115467
1986:1613457
1947:2440668
1910:27 July
1880:Netpath
1793:Decorin
1767:(ALK5)
1760:TGFβRII
1730:(ALK7)
1703:Chordin
1678:(ALK6)
1640:(ALK5)
1602:(ALK4)
1565:(ALK4)
1544:Co-SMAD
1540:R-SMADs
1429:insulin
1248:R-SMADs
1208:activin
1204:R-SMADs
1185:R-SMADs
1152:Co-SMAD
1146:SMAD8/9
1029:dimeric
972:calcium
855:In the
828:spindle
760:cancers
720:Patched
364:of the
205:of the
44:diffuse
4272:Agents
4140:(MeSH)
4114:
4075:
4065:
4026:
3985:
3944:
3905:131895
3903:
3895:
3860:
3853:149146
3850:
3811:
3783:Nature
3762:
3721:
3678:
3649:
3617:
3609:
3566:
3556:
3510:
3502:
3466:
3458:
3423:
3405:
3378:
3368:
3324:
3314:
3270:
3260:
3216:
3175:
3167:
3141:Nature
3124:
3083:
3073:
3034:
3026:
2985:
2950:
2909:
2901:
2863:
2814:
2773:
2728:
2718:
2679:
2671:
2635:
2599:
2558:
2517:
2509:
2463:
2453:
2389:
2385:,
2370:
2360:
2320:
2312:
2277:
2269:
2233:
2198:
2163:
2125:
2084:
2040:
2002:
1992:
1984:
1945:
1765:TGFβRI
1728:ACVR1C
1724:ACVR1B
1719:ACVR2B
1699:Noggin
1676:BMPR1B
1672:BMPR1A
1638:TGFβRI
1634:ACVR1B
1629:ACVR2B
1600:ACVR1B
1595:ACVR2A
1563:ACVR1B
1558:ACVR2A
1351:, and
1300:, and
1286:TGF-β3
1282:TGF-β2
1278:TGF-β1
1163:I-SMAD
1125:R-SMAD
1119:SMADs
1104:I-SMAD
1094:R-SMAD
1065:serine
1059:, and
1009:cancer
944:GTPase
934:, and
810:-rich
768:ligand
665:somite
565:Viable
554:Lethal
539:Viable
528:Lethal
517:Lethal
350:ligand
346:kinase
311:Viable
297:Lethal
280:Lethal
266:Lethal
252:Viable
238:Viable
203:retina
150:8 and
87:organs
62:; and
4434:TFIIH
4429:TFIID
4253:Hippo
4233:Notch
3901:S2CID
3615:S2CID
3508:S2CID
3464:S2CID
3173:S2CID
3032:S2CID
2907:S2CID
2677:S2CID
2515:S2CID
2408:with
2318:S2CID
2275:S2CID
1982:JSTOR
1789:THBS1
1785:LTBP1
1780:SMAD4
1775:SMAD3
1771:SMAD2
1755:TGFβs
1748:Lefty
1743:SMAD4
1738:SMAD3
1734:SMAD2
1714:Nodal
1694:SMAD4
1689:SMAD8
1685:SMAD5
1682:SMAD1
1667:BMPR2
1653:SMAD4
1648:SMAD3
1644:SMAD2
1624:GDF11
1615:SMAD4
1610:SMAD3
1606:SMAD2
1578:SMAD4
1573:SMAD3
1569:SMAD2
1489:Nodal
1252:SMAD4
1240:SMAD4
1236:SMAD5
1232:SMAD1
1228:SMAD3
1224:SMAD2
1214:, or
1212:Nodal
1189:SMAD4
1172:SMAD7
1168:SMAD6
1156:SMAD4
1142:SMAD5
1138:SMAD3
1134:SMAD2
1130:SMAD1
1116:Class
1033:TGF-β
897:actin
594:Stat1
562:Stat4
551:Stat3
536:Stat1
4204:GPCR
4112:ISBN
4097:text
4073:PMID
4047:Cell
4024:PMID
3983:PMID
3942:PMID
3893:PMID
3858:PMID
3809:PMID
3760:PMID
3719:PMID
3676:ISBN
3647:ISBN
3607:PMID
3564:PMID
3500:PMID
3456:PMID
3421:PMID
3376:PMID
3322:PMID
3268:PMID
3214:PMID
3165:PMID
3122:PMID
3081:PMID
3024:PMID
2983:PMID
2948:PMID
2899:PMID
2887:2007
2861:PMID
2835:and
2812:PMID
2771:PMID
2753:Cell
2726:PMID
2669:PMID
2653:Cell
2633:PMID
2597:PMID
2579:Cell
2556:PMID
2507:PMID
2461:PMID
2387:PMID
2368:PMID
2310:PMID
2267:PMID
2251:Cell
2231:PMID
2196:PMID
2161:PMID
2123:PMID
2082:PMID
2038:PMID
2000:PMID
1943:PMID
1912:2018
1808:and
1590:GDF1
1453:and
1431:and
1421:and
1396:BMP7
1394:and
1392:BMP4
1388:BMP7
1380:BMP4
1376:BMP7
1374:and
1372:BMP4
1315:and
1234:and
1226:and
1181:SMAD
1170:and
1144:and
1043:The
1007:and
986:. IP
899:and
869:GSK3
802:The
651:and
629:The
525:Jak2
514:Jak1
442:the
199:mRNA
170:10.
37:cell
4216:RTK
4211:Wnt
4146:at
4063:PMC
4055:doi
4051:134
4014:doi
4010:279
3973:doi
3932:doi
3928:118
3885:doi
3848:PMC
3840:doi
3799:doi
3787:388
3750:doi
3709:doi
3705:115
3599:doi
3587:296
3554:PMC
3544:doi
3492:doi
3448:doi
3444:129
3413:doi
3366:PMC
3358:doi
3312:PMC
3304:doi
3258:PMC
3250:doi
3246:329
3204:doi
3157:doi
3145:411
3112:doi
3071:PMC
3063:doi
3059:170
3014:doi
3010:140
2975:doi
2938:doi
2891:doi
2851:doi
2847:172
2837:Bmp
2802:doi
2761:doi
2757:107
2716:PMC
2708:doi
2704:119
2661:doi
2625:doi
2587:doi
2583:109
2546:doi
2542:117
2499:doi
2487:296
2451:PMC
2443:doi
2439:351
2379:doi
2358:PMC
2350:doi
2346:115
2302:doi
2259:doi
2223:doi
2188:doi
2153:doi
2113:doi
2109:130
2072:doi
2068:271
2030:doi
1990:PMC
1974:doi
1970:109
1935:doi
1707:DAN
1368:BMP
1025:TGF
873:APC
740:PKA
684:IHH
672:DHH
661:SHH
590:Fgf
474:),
386:Ras
380:An
306:Fgf
292:Fgf
275:Fgf
261:Fgf
247:Fgf
233:Fgf
195:fgf
188:Fgf
184:Fgf
180:Fgf
172:Fgf
168:Fgf
160:Tbx
152:Fgf
148:Fgf
100:Wnt
19:In
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