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mTORC2

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763:. Originally, mTORC2 was identified as a rapamycin-insensitive entity, as acute exposure to rapamycin did not affect mTORC2 activity or Akt phosphorylation. However, subsequent studies have shown that, at least in some cell lines, chronic exposure to rapamycin, while not affecting pre-existing mTORC2s, promotes rapamycin inhibition of free mTOR molecules, thus inhibiting the formation of new mTORC2. mTORC2 can be inhibited by chronic treatment with rapamycin 6086: 822:/PKC) protein kinase family. mTORC2 regulates actin cytoskeleton through PKCα but is able to phosphorylate other members of the PKC family that have various regulatory functions in cell migration and cytoskeletal remodeling. mTORC2 plays a pivotal role in phosphorylation and thus in activation of Akt, which is a vital signaling component downstream from PI3K once active, and also in phosphorylation of 843:. In many types of human cancer, hyperactivation of mTORC2 caused by mutations and aberrant amplifications of mTORC2 core components is frequently observed. On metabolic level, activation of mTORC2 stimulates processes related to alteration of glucose metabolism in cancer cells, altogether known as 838:
Since mTORC2 plays a crucial role in metabolic regulation, it can be linked to many human pathologies. Deregulation of mTOR signaling, including mTORC2, affects transduction of insulin signal and therefore can disrupt its biological functions and lead to metabolic disorders, such as
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in skeletal muscle results in decreased insulin-stimulated glucose uptake, and resistance to the effects of an mTOR kinase inhibitor on insulin resistance, highlighting a critical role for mTOR in the regulation of glucose homeostasis in this tissue. Loss of
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at the plasma membrane. mSin1 subunit can also be phosphorylated by Akt. This indicates the existence of a positive feedback loop in which partial activation of Akt stimulates the activation of mTORC2. The complex then phosphorylates and fully activates Akt.
2208:"Discovery of 1-(4-(4-propionylpiperazin-1-yl)-3-(trifluoromethyl)phenyl)-9-(quinolin-3-yl)benzo[h][1,6]naphthyridin-2(1H)-one as a highly potent, selective mammalian target of rapamycin (mTOR) inhibitor for the treatment of cancer" 1371:
Stephens L, Anderson K, Stokoe D, Erdjument-Bromage H, Painter GF, Holmes AB, et al. (January 1998). "Protein kinase B kinases that mediate phosphatidylinositol 3,4,5-trisphosphate-dependent activation of protein kinase B".
783:. This domain is vital for the insulin-dependent regulation of mTORC2 activity and inhibits the catalytic activity of mTORC2 in the absence of insulin. This autoinhibition is relieved upon binding to PI3K-generated 737:; however, this may be due to its association with Akt. It is not clear if these membranes display mTORC2 activity in the cellular context, or if these pools contribute to phosphorylation of mTORC2 substrates. 2721:
Jhanwar-Uniyal M, Amin AG, Cooper JB, Das K, Schmidt MH, Murali R (May 2017). "Discrete signaling mechanisms of mTORC1 and mTORC2: Connected yet apart in cellular and molecular aspects".
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Though less understood than mTORC1, mTORC2 has been shown to respond to growth factors and to modulate cell metabolism and cell survival, thanks to its activation of the survival kinase
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results in reduced beta cell mass and insulin secretion, and hyperglycemia and glucose intolerance. mTORC2 activity in the hypothalamus of mice increases with age, and deletion of
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leads to glucose intolerance, hepatic insulin resistance, decreased hepatic lipogenesis, and decreased male lifespan. Adipose-specific disruption of mTORC2 through deletion of
802:, a negative regulator of insulin/IGF-1 receptor signaling upstream of Akt and mTORC2, is phosphorylated and therefore activated by mTORC1. Additionally, some components of 1914:
Lin, Yiyan; Pal, Dhiman Sankar; Banerjee, Parijat; Banerjee, Tatsat; Qin, Guanghui; Deng, Yu; Borleis, Jane; Iglesias, Pablo A.; Devreotes, Peter N. (2024-07-01).
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mTORC2 appears to be regulated by insulin, growth factors, and serum. In contrast to TORC1, which is mainly stimulated by nutrients, TORC2 is mainly stimulated by
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remodeling. The complex itself is rather large, consisting of seven protein subunits. The catalytic mTOR subunit, DEP domain containing mTOR-interacting protein (
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Beevers CS, Li F, Liu L, Huang S (August 2006). "Curcumin inhibits the mammalian target of rapamycin-mediated signaling pathways in cancer cells".
1211:"Feature Article: mTOR complex 2-Akt signaling at mitochondria-associated endoplasmic reticulum membranes (MAM) regulates mitochondrial physiology" 430: 289: 205: 52: 5487: 5529: 4690: 3993: 5638: 1857:
Pal, Dhiman Sankar; Banerjee, Tatsat; Lin, Yiyan; de Trogoff, Félix; Borleis, Jane; Iglesias, Pablo A.; Devreotes, Peter N. (July 2023).
1660:"mTORC2 promotes type I insulin-like growth factor receptor and insulin receptor activation through the tyrosine kinase activity of mTOR" 1262:"Rictor, a novel binding partner of mTOR, defines a rapamycin-insensitive and raptor-independent pathway that regulates the cytoskeleton" 3095:"Lifespan extension without fertility reduction following dietary addition of the autophagy activator Torin1 in Drosophila melanogaster" 4376: 4263: 1320:
Sarbassov DD, Guertin DA, Ali SM, Sabatini DM (February 2005). "Phosphorylation and regulation of Akt/PKB by the rictor-mTOR complex".
4651: 605: 5624: 5443: 5089: 4685: 4675: 4670: 3980: 3962: 562: 1566:"mTOR/p70S6K signaling distinguishes routine, maintenance-level autophagy from autophagic cell death during influenza A infection" 923:
and insulin resistance in older mice. The role of mTORC2 in skeletal muscle has taken time to uncover, but genetic loss of mTORC2/
5726: 5607: 210: 5313: 4182: 3672:"Muscle-specific deletion of rictor impairs insulin-stimulated glucose transport and enhances Basal glycogen synthase activity" 435: 294: 702:
inhibits both by preventing phosphorylation of the serine. Moreover, mTORC2 activity has been implicated in the regulation of
57: 6116: 5377: 4352: 3623:"Fat cell-specific ablation of rictor in mice impairs insulin-regulated fat cell and whole-body glucose and lipid metabolism" 2631: 6121: 6111: 6106: 5633: 3272:"mTORC2 Activity Disrupts Lysosome Acidification in Systemic Lupus Erythematosus by Impairing Caspase-1 Cleavage of Rab39a" 3513:"Ovariectomy uncouples lifespan from metabolic health and reveals a sex-hormone-dependent role of hepatic mTORC2 in aging" 4167: 454: 313: 76: 725:
The precise localization of mTORC2 inside cells is still unclear. Some findings based on its activity point to cellular
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signalling has been revealed as important regulators of mTORC2 activity as Ric-8B protein and some lipid metabolites.
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What might come as a surprise is that mTORC2 signaling is also regulated by mTORC1. This is due to the presence of a
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with no reduction in fertility and Akt haploinsufficiency, an mTORC2 downstream target, extended lifespan in mice.
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Nojima A, Yamashita M, Yoshida Y, Shimizu I, Ichimiya H, Kamimura N, et al. (2013-07-30). Sadoshima J (ed.).
2807:"mTOR complex 2 controls glycolytic metabolism in glioblastoma through FoxO acetylation and upregulation of c-Myc" 5573: 5245: 4607: 4598: 2357:"The mTOR-regulated phosphoproteome reveals a mechanism of mTORC1-mediated inhibition of growth factor signaling" 612:) can only be found in mTORC2. Rictor has been shown to be the scaffold protein for substrate binding to mTORC2. 779:
Similar to other PI3K regulated proteins, mTORC2 has a mSin1 subunit, which contains a phosphoinositide-binding
6136: 2907:"A diverse array of cancer-associated MTOR mutations are hyperactivating and can predict rapamycin sensitivity" 690:
residue S473 as well as serine residue S450. Phosphorylation of the serine stimulates Akt phosphorylation at a
874:. By contrast, dietary administration of Torin1, a dual mTORC1/2 inhibitor, resulted in prolonged lifespan in 814:
mTORC2 controls cell survival and proliferation mainly through phosphorylation of several members of the AGC (
5961: 4988: 4485: 4476: 4133: 4079: 733:, as a possible site of mTORC2, whereas other suggest that the complex could be additionally located at the 37: 22: 2465:"Catecholamine-induced lipolysis causes mTOR complex dissociation and inhibits glucose uptake in adipocytes" 628:-dependent manner. The complex also plays a role as an important regulator in the organization of the actin 4176: 897: 711: 447: 306: 222: 3866:
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Arriola Apelo SI, Lin A, Brinkman JA, Meyer E, Morrison M, Tomasiewicz JL, et al. (2020-07-28).
844: 3819:"Rictor/mTORC2 is essential for maintaining a balance between beta-cell proliferation and cell size" 5956: 5910: 5853: 5413: 5404: 5355: 4121: 3966: 3921: 3719:
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Sarbassov DD, Ali SM, Kim DH, Guertin DA, Latek RR, Erdjument-Bromage H, et al. (July 2004).
624:. mTORC2 activation by growth factors is done through promotion of mTORC2-ribosome association in 6141: 5858: 5713: 5136: 3411:
Lamming DW, Demirkan G, Boylan JM, Mihaylova MM, Peng T, Ferreira J, et al. (January 2014).
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residues Y1131/1136 and Y1146/1151, respectively, leading to full activation of IGF-IR and InsR.
2102:"mTOR complex 2 is required for the development of prostate cancer induced by Pten loss in mice" 1967:"mSin1 is necessary for Akt/PKB phosphorylation, and its isoforms define three distinct mTORC2s" 893:(MLN-0128) have potential in the treatment of this disease and similar fibrotic lung diseases. 666:
mTORC2 also regulates cellular proliferation and metabolism, in part through the regulation of
2151:"Rapamycin-induced insulin resistance is mediated by mTORC2 loss and uncoupled from longevity" 1965:
Frias MA, Thoreen CC, Jaffe JD, Schroder W, Sculley T, Carr SA, Sabatini DM (September 2006).
907:, and thus inactive mTORC2, have found that mTORC2 plays a critical role in the regulation of 5879: 5798: 4412: 2149:
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359: 1859:"Actuation of single downstream nodes in growth factor network steers immune cell migration" 504: 363: 5951: 4979: 3721:"Acute mTOR inhibition induces insulin resistance and alters substrate utilization in vivo" 3575: 3321:"Hepatic mTORC2 activates glycolysis and lipogenesis through Akt, glucokinase, and SREBP1c" 3224: 3165: 3106: 2535: 2476: 2463:
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2524:"Glycerolipid signals alter mTOR complex 2 (mTORC2) to diminish insulin signaling" 2355:
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in hypothalamic neurons promotes obesity, frailty, and shorter lifespan in mice.
840: 715: 558: 330: 234: 93: 3021: 3004: 2856:"Weighing In on mTOR Complex 2 Signaling: The Expanding Role in Cell Metabolism" 2734: 1577: 851:
has been linked to promotion of hepatocellular carcinoma through stimulation of
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Proceedings of the National Academy of Sciences of the United States of America
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1529: 1370: 1208: 478: 337: 100: 3834: 3638: 2598: 2583:"mTORC2 signaling promotes skeletal growth and bone formation in mice" 2223: 1428: 6031: 6005: 4519: 3868:"Hypothalamic mTORC2 is essential for metabolic health and longevity" 1709:"mTOR: from growth signal integration to cancer, diabetes and ageing" 866:, chronic rapamycin treatment abrogates mTORC2 signaling, leading to 863: 803: 780: 703: 691: 660: 554: 2755: 2689: 2061:"Prolonged rapamycin treatment inhibits mTORC2 assembly and Akt/PKB" 1827: 1724: 1609:
Arias E, Koga H, Diaz A, Mocholi E, Patel B, Cuervo AM (July 2015).
600:), mammalian stress-activated protein kinase interacting protein 1 ( 6085: 4875: 4770: 4765: 4760: 2257:"PtdIns(3,4,5)P3-Dependent Activation of the mTORC2 Kinase Complex" 1611:"Lysosomal mTORC2/PHLPP1/Akt Regulate Chaperone-Mediated Autophagy" 1059:
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3-methyl-2-oxobutanoate dehydrogenase (acetyl-transferring) kinase
3865: 5534: 5512: 5507: 5497: 5492: 5294: 5289: 5284: 5279: 5274: 5259: 5254: 4905: 4870: 4109: 4104: 4099: 3061: 1110:"The Ras-ERK and PI3K-mTOR pathways: cross-talk and compensation" 768: 748: 633: 601: 423: 408: 2758:"mTORC1 and mTORC2 as regulators of cell metabolism in immunity" 459: 318: 81: 6044: 5814: 5764: 5759: 5754: 5749: 5744: 5739: 5734: 5685: 5680: 5675: 5670: 5665: 5648: 5643: 5517: 5502: 5453: 5448: 5433: 5428: 5423: 5418: 5392: 5387: 5382: 5370: 5348: 5343: 5235: 5210: 4885: 4710: 4705: 4700: 4695: 4680: 4524: 4461: 4456: 4451: 4427: 4253: 4248: 4222: 4217: 4212: 4202: 4197: 4187: 4027: 3958: 2632:"mTORC2 targets AGC kinases through Sin1-dependent recruitment" 919:
may protect from a high-fat diet in young mice, but results in
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activity and phosphorylates IGF-IR and insulin receptor at the
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The mTORC2 pathways plays a crucial role in pathogenesis of
682:. mTORC2 phosphorylates the serine/threonine protein kinase 5553: 5480: 5475: 5465: 5438: 5195: 5145: 5126: 5121: 5116: 5111: 5066: 5061: 5056: 5051: 4998: 4954: 4895: 4890: 4840: 4825: 4795: 4725: 4641: 4636: 4631: 4564: 4466: 4407: 4402: 4306: 4272: 4157: 4152: 4147: 4116: 4084: 4072: 4067: 4062: 4052: 4047: 3360:
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and the serum-and glucocorticoid-induced protein kinase
2804: 2462: 1807: 2521: 2414:"Depletion of Ric-8B leads to reduced mTORC2 activity" 1913: 1259: 6074: 3669: 3269: 2354: 1608: 3620: 3092: 3005:"mTORC2 Promotes Tumorigenesis via Lipid Synthesis" 2953: 2580: 1706: 963:"mTOR Signaling in Growth, Metabolism, and Disease" 3816: 3359: 1512:Ballesteros-Álvarez J, Andersen JK (August 2021). 2671: 1414: 1159:"Growing knowledge of the mTOR signaling network" 6098: 2205: 1651: 1514:"mTORC2: The other mTOR in autophagy regulation" 1009: 903:Studies using mice with tissue-specific loss of 798:loop between mTORC1 and insulin/PI3K signaling. 3210: 2254: 1803: 1801: 1707:Zoncu R, Efeyan A, Sabatini DM (January 2011). 1107: 3767: 1758:"Localization of mTORC2 activity inside cells" 1315: 1313: 1012:"mTOR signaling in growth control and disease" 960: 956: 954: 952: 5799: 3994:Non-specific serine/threonine protein kinases 3943: 3093:Mason JS, Wileman T, Chapman T (2018-01-12). 2954:Masui K, Cavenee WK, Mischel PS (July 2014). 2021: 1058: 889:, and inhibitors of its active site such as 604:), and protein observed with rictor 1 and 2 ( 3037: 2093: 2015: 1798: 1700: 1457: 1163:Seminars in Cell & Developmental Biology 1657: 1310: 1204: 1202: 1156: 1101: 1061:"Cryo-EM structure of human mTOR complex 2" 949: 896:Chronic mTORC2 activity may play a role in 754: 596:. Rapamycin-insensitive companion of mTOR ( 584:), mammalian lethal with sec-13 protein 8 ( 5806: 5792: 4377:Goodpasture-antigen-binding protein kinase 3950: 3936: 2853: 862:Although mTORC2 is acutely insensitive to 5090:Serine/threonine-specific protein kinases 4264:(isocitrate dehydrogenase (NADP+)) kinase 3981:Serine/threonine-specific protein kinases 3963:Serine/threonine-specific protein kinases 3920:at the U.S. National Library of Medicine 3891: 3842: 3793: 3744: 3695: 3646: 3597: 3587: 3538: 3528: 3487: 3438: 3428: 3387: 3377: 3336: 3295: 3246: 3236: 3187: 3177: 3128: 3118: 3069: 3020: 2979: 2930: 2881: 2871: 2860:Oxidative Medicine and Cellular Longevity 2830: 2781: 2697: 2606: 2557: 2547: 2498: 2488: 2439: 2429: 2388: 2331: 2321: 2280: 2231: 2182: 2125: 2076: 1990: 1890: 1781: 1732: 1683: 1634: 1585: 1537: 1483: 1285: 1236: 1226: 1182: 1133: 1108:Mendoza MC, Er EE, Blenis J (June 2011). 1084: 1035: 986: 5625:Receptor protein serine/threonine kinase 1559: 1557: 1199: 1003: 5608:Low-density-lipoprotein receptor kinase 2854:Luo Y, Xu W, Li G, Cui W (2018-10-30). 1408: 1364: 809: 6099: 3043: 2960:Trends in Endocrinology and Metabolism 1713:Nature Reviews. Molecular Cell Biology 1010:Laplante M, Sabatini DM (April 2012). 592:complex are shared by both mTORC2 and 5787: 5711: 5087: 4353:Fas-activated serine/threonine kinase 3978: 3931: 2052: 1958: 1602: 1554: 1507: 1505: 1503: 961:Saxton RA, Sabatini DM (March 2017). 774: 5725: 5634:Bone morphogenetic protein receptors 3768:Kennedy BK, Lamming DW (June 2016). 2587:Journal of Bone and Mineral Research 1253: 1157:Huang K, Fingar DC (December 2014). 771:can also be used to inhibit mTORC2. 744:and neutrophils, mTORC2 facilitates 4168:Dephospho-(reductase kinase) kinase 3366:The Journal of Biological Chemistry 2199: 13: 4623:G-protein coupled receptor kinases 1500: 1458:Yang Z, Klionsky DJ (April 2010). 833: 698:and leads to full Akt activation. 14: 6153: 4613:Beta adrenergic receptor kinase-2 4298:(tyrosine 3-monooxygenase) kinase 3911: 2723:Advances in Biological Regulation 1572:. 452–453 (March 2014): 175–190. 6084: 5305:Mitogen-activated protein kinase 900:by impairing lysosome function. 5691:Anti-Müllerian hormone receptor 5574:(acetyl-CoA carboxylase) kinase 5246:(RNA-polymerase)-subunit kinase 4608:Beta adrenergic receptor kinase 4599:Beta adrenergic receptor kinase 3859: 3810: 3761: 3712: 3663: 3614: 3555: 3504: 3455: 3404: 3353: 3312: 3263: 3204: 3145: 3086: 2996: 2947: 2898: 2847: 2798: 2749: 2714: 2665: 2623: 2574: 2515: 2456: 2405: 2348: 2297: 2248: 2142: 1907: 1850: 1749: 1464:Current Opinion in Cell Biology 1451: 1417:International Journal of Cancer 588:, also known as GβL), and TTI1/ 5314:Extracellular signal-regulated 3676:Molecular and Cellular Biology 2333:11858/00-001M-0000-0028-463C-B 2212:Journal of Medicinal Chemistry 1150: 1114:Trends in Biochemical Sciences 1052: 1: 5378:P38 mitogen-activated protein 4477:cGMP-dependent protein kinase 4438:cAMP-dependent protein kinase 4134:Pyruvate dehydrogenase kinase 4080:Ataxia telangiectasia mutated 943: 6117:Genes on human chromosome 16 4177:AMP-activated protein kinase 3737:10.1016/j.molmet.2014.06.004 3238:10.1371/journal.pone.0106155 3179:10.1371/journal.pone.0069178 3120:10.1371/journal.pone.0190105 2923:10.1158/2159-8290.CD-13-0929 2431:10.1371/journal.pgen.1008255 2323:10.1016/j.celrep.2015.07.016 2273:10.1158/2159-8290.CD-15-0460 2078:10.1016/j.molcel.2006.03.029 1875:10.1016/j.devcel.2023.04.019 1627:10.1016/j.molcel.2015.05.030 1394:10.1126/science.279.5351.710 1175:10.1016/j.semcdb.2014.09.011 898:systemic lupus erythematosus 712:chaperone-mediated autophagy 7: 6122:Genes on human chromosome 9 6112:Genes on human chromosome 5 6107:Genes on human chromosome 1 5813: 5092:(EC 2.7.11.21-EC 2.7.11.30) 3022:10.1016/j.ccell.2017.11.011 2735:10.1016/j.jbior.2016.12.001 1762:The Journal of Cell Biology 1578:10.1016/j.virol.2014.01.008 714:). In addition, mTORC2 has 632:through its stimulation of 615: 10: 6158: 5019:Elongation factor 2 kinase 3983:(EC 2.7.11.1-EC 2.7.11.20) 3786:10.1016/j.cmet.2016.05.009 3338:10.1016/j.cmet.2012.03.015 2823:10.1016/j.cmet.2013.09.013 2038:10.1152/physrev.00038.2014 1932:10.1038/s41556-024-01453-4 1126:10.1016/j.tibs.2011.03.006 1028:10.1016/j.cell.2012.03.017 979:10.1016/j.cell.2017.02.004 5970: 5962:Michaelis–Menten kinetics 5934: 5903: 5872: 5821: 5721: 5707: 5623: 5606: 5589: 5572: 5543: 5414:MAP kinase kinase kinases 5403: 5303: 5244: 5135: 5101: 5097: 5083: 5041: 5017: 4978: 4946:Myosin light-chain kinase 4944: 4652:Ca2+/calmodulin-dependent 4650: 4621: 4597: 4578: 4499: 4475: 4436: 4392: 4375: 4351: 4317:Myosin-heavy-chain kinase 4315: 4296: 4262: 4233: 4166: 4132: 3992: 3988: 3974: 2972:10.1016/j.tem.2014.04.002 2118:10.1016/j.ccr.2008.12.017 1992:10.1016/j.cub.2006.08.001 1476:10.1016/j.ceb.2009.11.014 1287:10.1016/j.cub.2004.06.054 1077:10.1038/s41422-018-0029-3 530: 520: 515: 511: 494: 489: 477: 465: 453: 441: 429: 419: 414: 407: 389: 379: 374: 370: 353: 348: 336: 324: 312: 300: 288: 278: 273: 266: 245: 240: 228: 216: 204: 194: 189: 182: 164: 154: 149: 145: 128: 116: 111: 99: 87: 75: 63: 51: 43: 33: 28: 21: 5854:Diffusion-limited enzyme 5714:Dual-specificity kinases 3922:Medical Subject Headings 3288:10.4049/jimmunol.1701712 841:type 2 diabetes mellitus 755:Regulation and signaling 5137:Cyclin-dependent kinase 3589:10.1073/pnas.0811321106 3379:10.1074/jbc.M112.386854 3050:Frontiers in Bioscience 2774:10.1002/1873-3468.12711 2639:The Biochemical Journal 2549:10.1073/pnas.1110730109 2490:10.1073/pnas.1410530111 2381:10.1126/science.1199498 2175:10.1126/science.1215135 1342:10.1126/science.1106148 1228:10.1073/pnas.1302455110 563:serine/threonine kinase 3044:Maiese K (June 2020). 6137:Tor signaling pathway 5947:Eadie–Hofstee diagram 5880:Allosteric regulation 3276:Journal of Immunology 2025:Physiological Reviews 1774:10.1083/jcb.201610060 934:pancreatic beta cells 5957:Lineweaver–Burk plot 4980:Phosphorylase kinase 3725:Molecular Metabolism 3688:10.1128/MCB.01405-07 3430:10.1096/fj.13-237743 2873:10.1155/2018/7838647 1869:(13): 1170–1188.e7. 810:Downstream signaling 3580:2009PNAS..106.9902C 3530:10.7554/eLife.56177 3229:2014PLoSO...9j6155C 3170:2013PLoSO...869178N 3111:2018PLoSO..1390105M 2678:Nature Cell Biology 2540:2012PNAS..109.1667Z 2481:2014PNAS..11117450M 2373:2011Sci...332.1317H 2167:2012Sci...335.1638L 1983:2006CBio...16.1865F 1920:Nature Cell Biology 1815:Nature Neuroscience 1676:10.1038/cr.2015.133 1386:1998Sci...279..710S 1334:2005Sci...307.1098S 1278:2004CBio...14.1296D 909:glucose homeostasis 872:glucose intolerance 853:glycerophospholipid 5916:Enzyme superfamily 5849:Enzyme promiscuity 5591:Tropomyosin kinase 5545:Tau-protein kinase 3884:10.1111/acel.13014 3480:10.1111/acel.12256 3015:(6): 807–823.e12. 2651:10.1042/BJ20110678 1863:Developmental Cell 1808:Costa-Mattioli M, 1530:10.1111/acel.13431 1328:(5712): 1098–101. 868:insulin resistance 847:. mTORC2-mediated 775:Upstream signaling 570:cell proliferation 47:FRAP, FRAP2, FRAP1 6127:Protein complexes 6072: 6071: 5781: 5780: 5777: 5776: 5773: 5772: 5703: 5702: 5699: 5698: 5079: 5078: 5075: 5074: 4560:Protein kinase N1 4515:Protein kinase Cζ 3835:10.2337/db10-1194 3639:10.2337/db09-1061 3056:(11): 1925–1973. 2768:(19): 3089–3103. 2599:10.1002/jbmr.2348 2367:(6035): 1317–22. 2224:10.1021/jm101144f 2161:(6076): 1638–43. 1822:(11): 1537–1543. 1429:10.1002/ijc.21932 921:hepatic steatosis 796:negative feedback 544: 543: 540: 539: 403: 402: 399: 398: 262: 261: 178: 177: 174: 173: 6149: 6089: 6088: 6080: 5952:Hanes–Woolf plot 5895:Enzyme activator 5890:Enzyme inhibitor 5864:Enzyme catalysis 5808: 5801: 5794: 5785: 5784: 5723: 5722: 5709: 5708: 5356:C-Jun N-terminal 5099: 5098: 5085: 5084: 4589:Rhodopsin kinase 4580:Rhodopsin kinase 4510:Protein kinase C 4501:Protein kinase C 4486:Protein kinase G 4447:Protein kinase A 4058:Protein kinase B 3990: 3989: 3976: 3975: 3952: 3945: 3938: 3929: 3928: 3906: 3905: 3895: 3863: 3857: 3856: 3846: 3814: 3808: 3807: 3797: 3765: 3759: 3758: 3748: 3716: 3710: 3709: 3699: 3667: 3661: 3660: 3650: 3618: 3612: 3611: 3601: 3591: 3559: 3553: 3552: 3542: 3532: 3508: 3502: 3501: 3491: 3459: 3453: 3452: 3442: 3432: 3408: 3402: 3401: 3391: 3381: 3372:(35): 29579–88. 3357: 3351: 3350: 3340: 3316: 3310: 3309: 3299: 3267: 3261: 3260: 3250: 3240: 3208: 3202: 3201: 3191: 3181: 3149: 3143: 3142: 3132: 3122: 3090: 3084: 3083: 3073: 3041: 3035: 3034: 3024: 3000: 2994: 2993: 2983: 2951: 2945: 2944: 2934: 2911:Cancer Discovery 2902: 2896: 2895: 2885: 2875: 2851: 2845: 2844: 2834: 2802: 2796: 2795: 2785: 2753: 2747: 2746: 2718: 2712: 2711: 2701: 2669: 2663: 2662: 2636: 2627: 2621: 2620: 2610: 2578: 2572: 2571: 2561: 2551: 2519: 2513: 2512: 2502: 2492: 2460: 2454: 2453: 2443: 2433: 2409: 2403: 2402: 2392: 2352: 2346: 2345: 2335: 2325: 2301: 2295: 2294: 2284: 2267:(11): 1194–209. 2261:Cancer Discovery 2252: 2246: 2245: 2235: 2203: 2197: 2196: 2186: 2146: 2140: 2139: 2129: 2097: 2091: 2090: 2080: 2056: 2050: 2049: 2032:(4): 1157–1187. 2019: 2013: 2012: 1994: 1962: 1956: 1955: 1946: 11364469. 1926:(7): 1062–1076. 1911: 1905: 1904: 1894: 1854: 1848: 1847: 1805: 1796: 1795: 1785: 1753: 1747: 1746: 1736: 1704: 1698: 1697: 1687: 1655: 1649: 1648: 1638: 1606: 1600: 1599: 1589: 1561: 1552: 1551: 1541: 1509: 1498: 1497: 1487: 1455: 1449: 1448: 1412: 1406: 1405: 1368: 1362: 1361: 1317: 1308: 1307: 1289: 1272:(14): 1296–302. 1257: 1251: 1250: 1240: 1230: 1221:(31): 12526–34. 1206: 1197: 1196: 1186: 1154: 1148: 1147: 1137: 1105: 1099: 1098: 1088: 1056: 1050: 1049: 1039: 1007: 1001: 1000: 990: 958: 694:T308 residue by 657:protein kinase C 553:) is an acutely 513: 512: 405: 404: 372: 371: 264: 263: 180: 179: 147: 146: 19: 18: 6157: 6156: 6152: 6151: 6150: 6148: 6147: 6146: 6097: 6096: 6095: 6083: 6075: 6073: 6068: 5980:Oxidoreductases 5966: 5942:Enzyme kinetics 5930: 5926:List of enzymes 5899: 5868: 5839:Catalytic triad 5817: 5812: 5782: 5769: 5717: 5695: 5619: 5602: 5585: 5568: 5539: 5399: 5299: 5270:P70-S6 Kinase 1 5240: 5131: 5093: 5071: 5037: 5013: 4974: 4940: 4646: 4617: 4593: 4574: 4495: 4471: 4432: 4388: 4371: 4347: 4341:Aurora C kinase 4336:Aurora B kinase 4331:Aurora A kinase 4311: 4292: 4258: 4229: 4162: 4128: 3984: 3970: 3956: 3914: 3909: 3864: 3860: 3815: 3811: 3780:(6): 990–1003. 3774:Cell Metabolism 3766: 3762: 3717: 3713: 3668: 3664: 3633:(6): 1397–406. 3619: 3615: 3560: 3556: 3509: 3505: 3460: 3456: 3409: 3405: 3358: 3354: 3325:Cell Metabolism 3317: 3313: 3268: 3264: 3209: 3205: 3150: 3146: 3105:(1): e0190105. 3091: 3087: 3042: 3038: 3001: 2997: 2952: 2948: 2903: 2899: 2852: 2848: 2811:Cell Metabolism 2803: 2799: 2754: 2750: 2719: 2715: 2690:10.1038/ncb2507 2670: 2666: 2634: 2628: 2624: 2579: 2575: 2520: 2516: 2475:(49): 17450–5. 2461: 2457: 2424:(5): e1008255. 2410: 2406: 2353: 2349: 2302: 2298: 2253: 2249: 2218:(19): 7146–55. 2204: 2200: 2147: 2143: 2098: 2094: 2057: 2053: 2020: 2016: 1977:(18): 1865–70. 1971:Current Biology 1963: 1959: 1912: 1908: 1855: 1851: 1828:10.1038/nn.3546 1806: 1799: 1754: 1750: 1725:10.1038/nrm3025 1705: 1701: 1656: 1652: 1607: 1603: 1562: 1555: 1510: 1501: 1456: 1452: 1413: 1409: 1380:(5351): 710–4. 1369: 1365: 1318: 1311: 1266:Current Biology 1258: 1254: 1207: 1200: 1155: 1151: 1106: 1102: 1057: 1053: 1008: 1004: 959: 950: 946: 836: 834:Role in disease 812: 788: 777: 757: 735:plasma membrane 716:tyrosine kinase 618: 568:that regulates 559:protein complex 17: 16:Protein complex 12: 11: 5: 6155: 6145: 6144: 6142:Human proteins 6139: 6134: 6129: 6124: 6119: 6114: 6109: 6094: 6093: 6070: 6069: 6067: 6066: 6053: 6040: 6027: 6014: 6001: 5988: 5974: 5972: 5968: 5967: 5965: 5964: 5959: 5954: 5949: 5944: 5938: 5936: 5932: 5931: 5929: 5928: 5923: 5918: 5913: 5907: 5905: 5904:Classification 5901: 5900: 5898: 5897: 5892: 5887: 5882: 5876: 5874: 5870: 5869: 5867: 5866: 5861: 5856: 5851: 5846: 5841: 5836: 5831: 5825: 5823: 5819: 5818: 5811: 5810: 5803: 5796: 5788: 5779: 5778: 5775: 5774: 5771: 5770: 5768: 5767: 5762: 5757: 5752: 5747: 5742: 5737: 5731: 5729: 5719: 5718: 5705: 5704: 5701: 5700: 5697: 5696: 5694: 5693: 5688: 5683: 5678: 5673: 5668: 5663: 5658: 5657: 5656: 5651: 5646: 5641: 5630: 5628: 5627:(EC 2.7.11.30) 5621: 5620: 5618: 5617: 5613: 5611: 5610:(EC 2.7.11.29) 5604: 5603: 5601: 5600: 5596: 5594: 5593:(EC 2.7.11.28) 5587: 5586: 5584: 5583: 5579: 5577: 5576:(EC 2.7.11.27) 5570: 5569: 5567: 5566: 5561: 5556: 5550: 5548: 5547:(EC 2.7.11.26) 5541: 5540: 5538: 5537: 5532: 5527: 5526: 5525: 5520: 5515: 5510: 5505: 5500: 5495: 5485: 5484: 5483: 5478: 5473: 5468: 5458: 5457: 5456: 5451: 5446: 5441: 5436: 5431: 5426: 5421: 5410: 5408: 5407:(EC 2.7.11.25) 5401: 5400: 5398: 5397: 5396: 5395: 5390: 5385: 5375: 5374: 5373: 5368: 5363: 5353: 5352: 5351: 5346: 5341: 5336: 5331: 5326: 5321: 5310: 5308: 5307:(EC 2.7.11.24) 5301: 5300: 5298: 5297: 5292: 5287: 5282: 5277: 5272: 5267: 5262: 5257: 5251: 5249: 5248:(EC 2.7.11.23) 5242: 5241: 5239: 5238: 5233: 5228: 5223: 5218: 5213: 5208: 5203: 5198: 5193: 5188: 5183: 5178: 5173: 5168: 5163: 5158: 5153: 5148: 5142: 5140: 5139:(EC 2.7.11.22) 5133: 5132: 5130: 5129: 5124: 5119: 5114: 5108: 5106: 5105:(EC 2.7.11.21) 5095: 5094: 5081: 5080: 5077: 5076: 5073: 5072: 5070: 5069: 5064: 5059: 5054: 5048: 5046: 5045:(EC 2.7.11.21) 5039: 5038: 5036: 5035: 5030: 5024: 5022: 5021:(EC 2.7.11.20) 5015: 5014: 5012: 5011: 5006: 5001: 4996: 4991: 4985: 4983: 4982:(EC 2.7.11.19) 4976: 4975: 4973: 4972: 4967: 4962: 4957: 4951: 4949: 4948:(EC 2.7.11.18) 4942: 4941: 4939: 4938: 4933: 4928: 4923: 4918: 4913: 4908: 4903: 4898: 4893: 4888: 4883: 4878: 4873: 4868: 4863: 4858: 4853: 4848: 4843: 4838: 4833: 4828: 4823: 4818: 4813: 4808: 4803: 4798: 4793: 4788: 4783: 4778: 4773: 4768: 4763: 4758: 4753: 4748: 4743: 4738: 4733: 4728: 4723: 4718: 4713: 4708: 4703: 4698: 4693: 4688: 4683: 4678: 4673: 4668: 4663: 4657: 4655: 4654:(EC 2.7.11.17) 4648: 4647: 4645: 4644: 4639: 4634: 4628: 4626: 4625:(EC 2.7.11.16) 4619: 4618: 4616: 4615: 4610: 4604: 4602: 4601:(EC 2.7.11.15) 4595: 4594: 4592: 4591: 4585: 4583: 4582:(EC 2.7.11.14) 4576: 4575: 4573: 4572: 4567: 4562: 4557: 4552: 4547: 4542: 4537: 4532: 4527: 4522: 4517: 4512: 4506: 4504: 4503:(EC 2.7.11.13) 4497: 4496: 4494: 4493: 4488: 4482: 4480: 4479:(EC 2.7.11.12) 4473: 4472: 4470: 4469: 4464: 4459: 4454: 4449: 4443: 4441: 4440:(EC 2.7.11.11) 4434: 4433: 4431: 4430: 4425: 4420: 4415: 4410: 4405: 4399: 4397: 4396:(EC 2.7.11.10) 4390: 4389: 4387: 4386: 4382: 4380: 4373: 4372: 4370: 4369: 4364: 4358: 4356: 4349: 4348: 4346: 4345: 4344: 4343: 4338: 4333: 4322: 4320: 4313: 4312: 4310: 4309: 4303: 4301: 4294: 4293: 4291: 4290: 4285: 4280: 4275: 4269: 4267: 4260: 4259: 4257: 4256: 4251: 4246: 4240: 4238: 4231: 4230: 4228: 4227: 4226: 4225: 4220: 4215: 4207: 4206: 4205: 4200: 4192: 4191: 4190: 4185: 4173: 4171: 4164: 4163: 4161: 4160: 4155: 4150: 4145: 4139: 4137: 4130: 4129: 4127: 4126: 4125: 4124: 4114: 4113: 4112: 4107: 4102: 4097: 4087: 4082: 4077: 4076: 4075: 4070: 4065: 4055: 4050: 4045: 4040: 4035: 4030: 4025: 4020: 4015: 4010: 4005: 3999: 3997: 3986: 3985: 3972: 3971: 3955: 3954: 3947: 3940: 3932: 3926: 3925: 3913: 3912:External links 3910: 3908: 3907: 3858: 3809: 3760: 3711: 3662: 3613: 3574:(24): 9902–7. 3554: 3503: 3454: 3403: 3352: 3311: 3282:(2): 371–382. 3262: 3223:(8): e106155. 3203: 3144: 3085: 3036: 2995: 2946: 2897: 2846: 2797: 2748: 2713: 2664: 2622: 2573: 2534:(5): 1667–72. 2514: 2455: 2404: 2347: 2296: 2247: 2198: 2141: 2092: 2065:Molecular Cell 2051: 2014: 1957: 1906: 1849: 1797: 1768:(2): 343–353. 1748: 1699: 1650: 1615:Molecular Cell 1601: 1553: 1499: 1450: 1407: 1363: 1309: 1252: 1198: 1149: 1100: 1071:(5): 518–528. 1051: 1002: 973:(6): 960–976. 947: 945: 942: 845:Warburg effect 835: 832: 811: 808: 786: 776: 773: 761:growth factors 756: 753: 749:polymerization 708:macroautophagy 617: 614: 574:cell migration 572:and survival, 547:mTOR Complex 2 542: 541: 538: 537: 532: 528: 527: 522: 518: 517: 509: 508: 498: 492: 491: 487: 486: 481: 475: 474: 472:NM_001006617.1 469: 463: 462: 457: 451: 450: 445: 439: 438: 433: 427: 426: 421: 417: 416: 412: 411: 401: 400: 397: 396: 391: 387: 386: 381: 377: 376: 368: 367: 357: 351: 350: 346: 345: 340: 334: 333: 328: 322: 321: 316: 310: 309: 304: 298: 297: 292: 286: 285: 280: 276: 275: 271: 270: 260: 259: 249: 243: 242: 238: 237: 232: 226: 225: 220: 214: 213: 208: 202: 201: 196: 192: 191: 187: 186: 176: 175: 172: 171: 166: 162: 161: 156: 152: 151: 143: 142: 132: 126: 125: 120: 114: 113: 109: 108: 103: 97: 96: 91: 85: 84: 79: 73: 72: 67: 61: 60: 55: 49: 48: 45: 41: 40: 35: 31: 30: 26: 25: 15: 9: 6: 4: 3: 2: 6154: 6143: 6140: 6138: 6135: 6133: 6130: 6128: 6125: 6123: 6120: 6118: 6115: 6113: 6110: 6108: 6105: 6104: 6102: 6092: 6087: 6082: 6081: 6078: 6064: 6060: 6059: 6054: 6051: 6047: 6046: 6041: 6038: 6034: 6033: 6028: 6025: 6021: 6020: 6015: 6012: 6008: 6007: 6002: 5999: 5995: 5994: 5989: 5986: 5982: 5981: 5976: 5975: 5973: 5969: 5963: 5960: 5958: 5955: 5953: 5950: 5948: 5945: 5943: 5940: 5939: 5937: 5933: 5927: 5924: 5922: 5921:Enzyme family 5919: 5917: 5914: 5912: 5909: 5908: 5906: 5902: 5896: 5893: 5891: 5888: 5886: 5885:Cooperativity 5883: 5881: 5878: 5877: 5875: 5871: 5865: 5862: 5860: 5857: 5855: 5852: 5850: 5847: 5845: 5844:Oxyanion hole 5842: 5840: 5837: 5835: 5832: 5830: 5827: 5826: 5824: 5820: 5816: 5809: 5804: 5802: 5797: 5795: 5790: 5789: 5786: 5766: 5763: 5761: 5758: 5756: 5753: 5751: 5748: 5746: 5743: 5741: 5738: 5736: 5733: 5732: 5730: 5728: 5724: 5720: 5715: 5710: 5706: 5692: 5689: 5687: 5684: 5682: 5679: 5677: 5674: 5672: 5669: 5667: 5664: 5662: 5659: 5655: 5652: 5650: 5647: 5645: 5642: 5640: 5637: 5636: 5635: 5632: 5631: 5629: 5626: 5622: 5615: 5614: 5612: 5609: 5605: 5598: 5597: 5595: 5592: 5588: 5581: 5580: 5578: 5575: 5571: 5565: 5562: 5560: 5557: 5555: 5552: 5551: 5549: 5546: 5542: 5536: 5533: 5531: 5528: 5524: 5521: 5519: 5516: 5514: 5511: 5509: 5506: 5504: 5501: 5499: 5496: 5494: 5491: 5490: 5489: 5486: 5482: 5479: 5477: 5474: 5472: 5469: 5467: 5464: 5463: 5462: 5459: 5455: 5452: 5450: 5447: 5445: 5442: 5440: 5437: 5435: 5432: 5430: 5427: 5425: 5422: 5420: 5417: 5416: 5415: 5412: 5411: 5409: 5406: 5402: 5394: 5391: 5389: 5386: 5384: 5381: 5380: 5379: 5376: 5372: 5369: 5367: 5364: 5362: 5359: 5358: 5357: 5354: 5350: 5347: 5345: 5342: 5340: 5337: 5335: 5332: 5330: 5327: 5325: 5322: 5320: 5317: 5316: 5315: 5312: 5311: 5309: 5306: 5302: 5296: 5293: 5291: 5288: 5286: 5283: 5281: 5278: 5276: 5273: 5271: 5268: 5266: 5263: 5261: 5258: 5256: 5253: 5252: 5250: 5247: 5243: 5237: 5234: 5232: 5229: 5227: 5224: 5222: 5219: 5217: 5214: 5212: 5209: 5207: 5204: 5202: 5199: 5197: 5194: 5192: 5189: 5187: 5184: 5182: 5179: 5177: 5174: 5172: 5169: 5167: 5164: 5162: 5159: 5157: 5154: 5152: 5149: 5147: 5144: 5143: 5141: 5138: 5134: 5128: 5125: 5123: 5120: 5118: 5115: 5113: 5110: 5109: 5107: 5104: 5100: 5096: 5091: 5086: 5082: 5068: 5065: 5063: 5060: 5058: 5055: 5053: 5050: 5049: 5047: 5044: 5040: 5034: 5031: 5029: 5026: 5025: 5023: 5020: 5016: 5010: 5007: 5005: 5002: 5000: 4997: 4995: 4992: 4990: 4987: 4986: 4984: 4981: 4977: 4971: 4968: 4966: 4963: 4961: 4958: 4956: 4953: 4952: 4950: 4947: 4943: 4937: 4934: 4932: 4929: 4927: 4924: 4922: 4919: 4917: 4914: 4912: 4909: 4907: 4904: 4902: 4899: 4897: 4894: 4892: 4889: 4887: 4884: 4882: 4879: 4877: 4874: 4872: 4869: 4867: 4864: 4862: 4859: 4857: 4854: 4852: 4849: 4847: 4844: 4842: 4839: 4837: 4834: 4832: 4829: 4827: 4824: 4822: 4819: 4817: 4814: 4812: 4809: 4807: 4804: 4802: 4799: 4797: 4794: 4792: 4789: 4787: 4784: 4782: 4779: 4777: 4774: 4772: 4769: 4767: 4764: 4762: 4759: 4757: 4754: 4752: 4749: 4747: 4744: 4742: 4739: 4737: 4734: 4732: 4729: 4727: 4724: 4722: 4719: 4717: 4714: 4712: 4709: 4707: 4704: 4702: 4699: 4697: 4694: 4692: 4689: 4687: 4684: 4682: 4679: 4677: 4674: 4672: 4669: 4667: 4664: 4662: 4659: 4658: 4656: 4653: 4649: 4643: 4640: 4638: 4635: 4633: 4630: 4629: 4627: 4624: 4620: 4614: 4611: 4609: 4606: 4605: 4603: 4600: 4596: 4590: 4587: 4586: 4584: 4581: 4577: 4571: 4568: 4566: 4563: 4561: 4558: 4556: 4553: 4551: 4548: 4546: 4543: 4541: 4538: 4536: 4533: 4531: 4528: 4526: 4523: 4521: 4518: 4516: 4513: 4511: 4508: 4507: 4505: 4502: 4498: 4492: 4489: 4487: 4484: 4483: 4481: 4478: 4474: 4468: 4465: 4463: 4460: 4458: 4455: 4453: 4450: 4448: 4445: 4444: 4442: 4439: 4435: 4429: 4426: 4424: 4421: 4419: 4416: 4414: 4411: 4409: 4406: 4404: 4401: 4400: 4398: 4395: 4391: 4384: 4383: 4381: 4379:(EC 2.7.11.9) 4378: 4374: 4368: 4365: 4363: 4360: 4359: 4357: 4355:(EC 2.7.11.8) 4354: 4350: 4342: 4339: 4337: 4334: 4332: 4329: 4328: 4327: 4326:Aurora kinase 4324: 4323: 4321: 4319:(EC 2.7.11.7) 4318: 4314: 4308: 4305: 4304: 4302: 4300:(EC 2.7.11.6) 4299: 4295: 4289: 4286: 4284: 4281: 4279: 4276: 4274: 4271: 4270: 4268: 4266:(EC 2.7.11.5) 4265: 4261: 4255: 4252: 4250: 4247: 4245: 4242: 4241: 4239: 4237:(EC 2.7.11.4) 4236: 4232: 4224: 4221: 4219: 4216: 4214: 4211: 4210: 4208: 4204: 4201: 4199: 4196: 4195: 4193: 4189: 4186: 4184: 4181: 4180: 4178: 4175: 4174: 4172: 4170:(EC 2.7.11.3) 4169: 4165: 4159: 4156: 4154: 4151: 4149: 4146: 4144: 4141: 4140: 4138: 4136:(EC 2.7.11.2) 4135: 4131: 4123: 4120: 4119: 4118: 4115: 4111: 4108: 4106: 4103: 4101: 4098: 4096: 4093: 4092: 4091: 4090:EIF-2 kinases 4088: 4086: 4083: 4081: 4078: 4074: 4071: 4069: 4066: 4064: 4061: 4060: 4059: 4056: 4054: 4051: 4049: 4046: 4044: 4041: 4039: 4036: 4034: 4031: 4029: 4026: 4024: 4021: 4019: 4016: 4014: 4011: 4009: 4006: 4004: 4001: 4000: 3998: 3996:(EC 2.7.11.1) 3995: 3991: 3987: 3982: 3977: 3973: 3968: 3964: 3960: 3953: 3948: 3946: 3941: 3939: 3934: 3933: 3930: 3923: 3919: 3918:TOR+complex+2 3916: 3915: 3903: 3899: 3894: 3889: 3885: 3881: 3878:(5): e13014. 3877: 3873: 3869: 3862: 3854: 3850: 3845: 3840: 3836: 3832: 3829:(3): 827–37. 3828: 3824: 3820: 3813: 3805: 3801: 3796: 3791: 3787: 3783: 3779: 3775: 3771: 3764: 3756: 3752: 3747: 3742: 3738: 3734: 3731:(6): 630–41. 3730: 3726: 3722: 3715: 3707: 3703: 3698: 3693: 3689: 3685: 3681: 3677: 3673: 3666: 3658: 3654: 3649: 3644: 3640: 3636: 3632: 3628: 3624: 3617: 3609: 3605: 3600: 3595: 3590: 3585: 3581: 3577: 3573: 3569: 3565: 3558: 3550: 3546: 3541: 3536: 3531: 3526: 3522: 3518: 3514: 3507: 3499: 3495: 3490: 3485: 3481: 3477: 3473: 3469: 3465: 3458: 3450: 3446: 3441: 3436: 3431: 3426: 3423:(1): 300–15. 3422: 3418: 3417:FASEB Journal 3414: 3407: 3399: 3395: 3390: 3385: 3380: 3375: 3371: 3367: 3363: 3356: 3348: 3344: 3339: 3334: 3331:(5): 725–38. 3330: 3326: 3322: 3315: 3307: 3303: 3298: 3293: 3289: 3285: 3281: 3277: 3273: 3266: 3258: 3254: 3249: 3244: 3239: 3234: 3230: 3226: 3222: 3218: 3214: 3207: 3199: 3195: 3190: 3185: 3180: 3175: 3171: 3167: 3164:(7): e69178. 3163: 3159: 3155: 3148: 3140: 3136: 3131: 3126: 3121: 3116: 3112: 3108: 3104: 3100: 3096: 3089: 3081: 3077: 3072: 3067: 3063: 3059: 3055: 3051: 3047: 3040: 3032: 3028: 3023: 3018: 3014: 3010: 3006: 2999: 2991: 2987: 2982: 2977: 2973: 2969: 2966:(7): 364–73. 2965: 2961: 2957: 2950: 2942: 2938: 2933: 2928: 2924: 2920: 2917:(5): 554–63. 2916: 2912: 2908: 2901: 2893: 2889: 2884: 2879: 2874: 2869: 2865: 2861: 2857: 2850: 2842: 2838: 2833: 2828: 2824: 2820: 2817:(5): 726–39. 2816: 2812: 2808: 2801: 2793: 2789: 2784: 2779: 2775: 2771: 2767: 2763: 2759: 2752: 2744: 2740: 2736: 2732: 2728: 2724: 2717: 2709: 2705: 2700: 2695: 2691: 2687: 2684:(7): 686–96. 2683: 2679: 2675: 2668: 2660: 2656: 2652: 2648: 2645:(2): 287–97. 2644: 2640: 2633: 2626: 2618: 2614: 2609: 2604: 2600: 2596: 2593:(2): 369–78. 2592: 2588: 2584: 2577: 2569: 2565: 2560: 2555: 2550: 2545: 2541: 2537: 2533: 2529: 2525: 2518: 2510: 2506: 2501: 2496: 2491: 2486: 2482: 2478: 2474: 2470: 2466: 2459: 2451: 2447: 2442: 2437: 2432: 2427: 2423: 2419: 2418:PLOS Genetics 2415: 2408: 2400: 2396: 2391: 2386: 2382: 2378: 2374: 2370: 2366: 2362: 2358: 2351: 2343: 2339: 2334: 2329: 2324: 2319: 2316:(6): 937–43. 2315: 2311: 2307: 2300: 2292: 2288: 2283: 2278: 2274: 2270: 2266: 2262: 2258: 2251: 2243: 2239: 2234: 2229: 2225: 2221: 2217: 2213: 2209: 2202: 2194: 2190: 2185: 2180: 2176: 2172: 2168: 2164: 2160: 2156: 2152: 2145: 2137: 2133: 2128: 2123: 2119: 2115: 2112:(2): 148–59. 2111: 2107: 2103: 2096: 2088: 2084: 2079: 2074: 2071:(2): 159–68. 2070: 2066: 2062: 2055: 2047: 2043: 2039: 2035: 2031: 2027: 2026: 2018: 2010: 2006: 2002: 1998: 1993: 1988: 1984: 1980: 1976: 1972: 1968: 1961: 1953: 1949: 1945: 1941: 1937: 1933: 1929: 1925: 1921: 1917: 1910: 1902: 1898: 1893: 1888: 1884: 1880: 1876: 1872: 1868: 1864: 1860: 1853: 1845: 1841: 1837: 1833: 1829: 1825: 1821: 1817: 1816: 1811: 1804: 1802: 1793: 1789: 1784: 1779: 1775: 1771: 1767: 1763: 1759: 1752: 1744: 1740: 1735: 1730: 1726: 1722: 1718: 1714: 1710: 1703: 1695: 1691: 1686: 1681: 1677: 1673: 1669: 1665: 1664:Cell Research 1661: 1654: 1646: 1642: 1637: 1632: 1628: 1624: 1621:(2): 270–84. 1620: 1616: 1612: 1605: 1597: 1593: 1588: 1583: 1579: 1575: 1571: 1567: 1560: 1558: 1549: 1545: 1540: 1535: 1531: 1527: 1524:(8): e13431. 1523: 1519: 1515: 1508: 1506: 1504: 1495: 1491: 1486: 1481: 1477: 1473: 1470:(2): 124–31. 1469: 1465: 1461: 1454: 1446: 1442: 1438: 1434: 1430: 1426: 1423:(4): 757–64. 1422: 1418: 1411: 1403: 1399: 1395: 1391: 1387: 1383: 1379: 1375: 1367: 1359: 1355: 1351: 1347: 1343: 1339: 1335: 1331: 1327: 1323: 1316: 1314: 1305: 1301: 1297: 1293: 1288: 1283: 1279: 1275: 1271: 1267: 1263: 1256: 1248: 1244: 1239: 1234: 1229: 1224: 1220: 1216: 1212: 1205: 1203: 1194: 1190: 1185: 1180: 1176: 1172: 1168: 1164: 1160: 1153: 1145: 1141: 1136: 1131: 1127: 1123: 1119: 1115: 1111: 1104: 1096: 1092: 1087: 1082: 1078: 1074: 1070: 1066: 1065:Cell Research 1062: 1055: 1047: 1043: 1038: 1033: 1029: 1025: 1022:(2): 274–93. 1021: 1017: 1013: 1006: 998: 994: 989: 984: 980: 976: 972: 968: 964: 957: 955: 953: 948: 941: 939: 935: 931: 926: 922: 918: 914: 910: 906: 901: 899: 894: 892: 888: 887:lung fibrosis 883: 881: 877: 873: 869: 865: 860: 858: 854: 850: 846: 842: 831: 829: 825: 821: 817: 807: 805: 801: 797: 792: 789: 782: 772: 770: 766: 762: 752: 750: 747: 743: 738: 736: 732: 729:, such as of 728: 727:endomembranes 723: 721: 717: 713: 709: 705: 701: 697: 693: 689: 685: 681: 677: 673: 669: 664: 662: 658: 654: 650: 646: 642: 638: 637:stress fibers 635: 631: 627: 623: 613: 611: 607: 603: 599: 595: 591: 587: 583: 579: 575: 571: 567: 564: 560: 557:-insensitive 556: 552: 548: 536: 533: 529: 526: 523: 519: 514: 510: 507: 506: 502: 499: 497: 493: 488: 485: 482: 480: 476: 473: 470: 468: 464: 461: 458: 456: 452: 449: 446: 444: 440: 437: 434: 432: 428: 425: 422: 418: 413: 410: 406: 395: 392: 388: 385: 382: 378: 373: 369: 366: 365: 361: 358: 356: 352: 347: 344: 341: 339: 335: 332: 329: 327: 323: 320: 317: 315: 311: 308: 305: 303: 299: 296: 293: 291: 287: 284: 281: 277: 272: 269: 265: 258: 257: 253: 250: 248: 244: 239: 236: 233: 231: 227: 224: 221: 219: 215: 212: 209: 207: 203: 200: 197: 193: 188: 185: 181: 170: 167: 163: 160: 157: 153: 148: 144: 141: 140: 136: 133: 131: 127: 124: 121: 119: 115: 110: 107: 104: 102: 98: 95: 92: 90: 86: 83: 80: 78: 74: 71: 68: 66: 62: 59: 56: 54: 50: 46: 42: 39: 36: 32: 27: 24: 20: 6058:Translocases 6055: 6042: 6029: 6016: 6003: 5993:Transferases 5990: 5977: 5834:Binding site 5265:P70S6 kinase 3875: 3871: 3861: 3826: 3822: 3812: 3777: 3773: 3763: 3728: 3724: 3714: 3682:(1): 61–70. 3679: 3675: 3665: 3630: 3626: 3616: 3571: 3567: 3557: 3520: 3516: 3506: 3474:(5): 911–7. 3471: 3467: 3457: 3420: 3416: 3406: 3369: 3365: 3355: 3328: 3324: 3314: 3279: 3275: 3265: 3220: 3216: 3206: 3161: 3157: 3147: 3102: 3098: 3088: 3062:10.2741/4886 3053: 3049: 3039: 3012: 3008: 2998: 2963: 2959: 2949: 2914: 2910: 2900: 2863: 2859: 2849: 2814: 2810: 2800: 2765: 2762:FEBS Letters 2761: 2751: 2726: 2722: 2716: 2681: 2677: 2667: 2642: 2638: 2625: 2590: 2586: 2576: 2531: 2527: 2517: 2472: 2468: 2458: 2421: 2417: 2407: 2364: 2360: 2350: 2313: 2310:Cell Reports 2309: 2299: 2264: 2260: 2250: 2215: 2211: 2201: 2158: 2154: 2144: 2109: 2105: 2095: 2068: 2064: 2054: 2029: 2023: 2017: 1974: 1970: 1960: 1923: 1919: 1909: 1866: 1862: 1852: 1819: 1813: 1810:Monteggia LM 1765: 1761: 1751: 1719:(1): 21–35. 1716: 1712: 1702: 1670:(1): 46–65. 1667: 1663: 1653: 1618: 1614: 1604: 1569: 1521: 1517: 1467: 1463: 1453: 1420: 1416: 1410: 1377: 1373: 1366: 1325: 1321: 1269: 1265: 1255: 1218: 1214: 1166: 1162: 1152: 1120:(6): 320–8. 1117: 1113: 1103: 1068: 1064: 1054: 1019: 1015: 1005: 970: 966: 937: 929: 924: 916: 912: 904: 902: 895: 891:sapanisertib 884: 880:melanogaster 879: 875: 861: 857:sphingolipid 837: 813: 793: 778: 764: 758: 739: 731:mitochondria 724: 665: 630:cytoskeleton 619: 578:cytoskeletal 550: 546: 545: 503: 362: 254: 137: 44:Alt. symbols 5829:Active site 5716:(EC 2.7.12) 5103:Polo kinase 5043:Polo kinase 3009:Cancer Cell 2866:: 7838647. 2106:Cancer Cell 859:synthesis. 849:lipogenesis 826:, PKC and 525:Swiss-model 415:Identifiers 384:Swiss-model 274:Identifiers 190:Identifiers 159:Swiss-model 29:Identifiers 6101:Categories 6032:Isomerases 6006:Hydrolases 5873:Regulation 4394:IκB kinase 3969:2.7.11-12) 3872:Aging Cell 3523:: e56177. 3468:Aging Cell 1518:Aging Cell 944:References 561:formed by 521:Structures 516:Search for 490:Other data 380:Structures 375:Search for 349:Other data 241:Other data 155:Structures 150:Search for 112:Other data 6132:EC 2.7.11 5911:EC number 4520:PKC alpha 2729:: 39–48. 1940:1476-4679 1883:1534-5807 1169:: 79–90. 864:rapamycin 804:G protein 781:PH domain 704:autophagy 692:threonine 555:rapamycin 431:NCBI gene 331:NM_022372 290:NCBI gene 235:NM_152756 206:NCBI gene 118:EC number 94:NM_004958 53:NCBI gene 5935:Kinetics 5859:Cofactor 5822:Activity 4876:KIAA0999 4771:MAPKAPK5 4766:MAPKAPK3 4761:MAPKAPK2 3902:31373126 3853:21266327 3823:Diabetes 3804:27304501 3755:25161886 3706:17967879 3657:20332342 3627:Diabetes 3608:19497867 3549:32720643 3498:25059582 3449:24072782 3398:22773877 3347:22521878 3306:29866702 3257:25162417 3217:PLOS ONE 3198:23935948 3158:PLOS ONE 3139:29329306 3099:PLOS ONE 3080:32472766 3031:29232555 2990:24856037 2941:24631838 2892:30510625 2841:24140020 2792:28600802 2743:28189457 2708:22609986 2659:21806543 2617:25196701 2568:22307628 2509:25422441 2450:32392211 2399:21659604 2342:26235620 2291:26293922 2242:20860370 2193:22461615 2136:19185849 2087:16603397 2046:26269525 2001:16919458 1952:38951708 1901:37220748 1892:10524337 1836:24165680 1792:28143890 1743:21157483 1694:26584640 1645:26118642 1596:24606695 1570:Virology 1548:34250734 1494:20034776 1445:25454463 1437:16550606 1358:45837814 1350:15718470 1296:15268862 1247:23852728 1193:25242279 1144:21531565 1095:29567957 1046:22500797 997:28283069 720:tyrosine 700:Curcumin 641:paxillin 616:Function 535:InterPro 394:InterPro 169:InterPro 123:2.7.11.1 6091:Biology 6045:Ligases 5815:Enzymes 5535:MAP3K14 5513:MAP3K11 5508:MAP3K10 5498:MAP3K13 5493:MAP3K12 5295:RPS6KC1 5290:RPS6KA1 5285:RPS6KA3 5280:RPS6KA2 5275:RPS6KB2 5260:RPS6KA4 5255:RPS6KA5 4906:Kalirin 4871:SNF1LK2 4110:EIF2AK4 4105:EIF2AK3 3959:Kinases 3924:(MeSH)} 3893:6718533 3844:3046843 3795:4910876 3746:4142396 3697:2223287 3648:2874700 3599:2700987 3576:Bibcode 3540:7386906 3489:4172536 3440:3868844 3389:3436168 3297:6039264 3248:4146613 3225:Bibcode 3189:3728301 3166:Bibcode 3130:5766080 3107:Bibcode 3071:7265993 2981:4077930 2932:4012430 2883:6232796 2832:3840163 2783:6322652 2699:3389271 2608:4322759 2559:3277174 2536:Bibcode 2500:4267365 2477:Bibcode 2441:7252638 2390:3177140 2369:Bibcode 2361:Science 2282:4631654 2233:3893826 2184:3324089 2163:Bibcode 2155:Science 2127:2701381 2009:8239162 1979:Bibcode 1844:7820105 1783:5294791 1734:3390257 1685:4816127 1636:4506737 1587:4005847 1539:8373318 1485:2854249 1402:9445477 1382:Bibcode 1374:Science 1330:Bibcode 1322:Science 1304:4658268 1274:Bibcode 1238:3732980 1184:4253687 1135:3112285 1086:5951902 1037:3331679 988:5394987 928:mTORC2/ 769:Torin-1 765:in vivo 742:neurons 684:Akt/PKB 676:Akt/PKB 634:F-actin 606:Protor1 531:Domains 479:UniProt 424:MAPKAP1 409:MAPKAP1 390:Domains 360:Chr. 16 338:UniProt 165:Domains 101:UniProt 6077:Portal 6019:Lyases 5765:MAP2K7 5760:MAP2K6 5755:MAP2K5 5750:MAP2K4 5745:MAP2K3 5740:MAP2K2 5735:MAP2K1 5686:ACVRL1 5681:ACVR2B 5676:ACVR2A 5671:ACVR1C 5666:ACVR1B 5649:BMPR1B 5644:BMPR1A 5518:MAP3K7 5503:MAP3K9 5454:MAP3K8 5449:MAP3K7 5444:MAP3K6 5439:MAP3K5 5434:MAP3K4 5429:MAP3K3 5424:MAP3K2 5419:MAP3K1 5393:MAPK14 5388:MAPK13 5383:MAPK11 5371:MAPK10 5349:MAPK15 5344:MAPK12 5236:CDC2L1 5211:CDC2L5 4886:SNF1LK 4711:CAMK2G 4706:CAMK2D 4701:CAMK2B 4696:CAMK2A 4686:CAMK1G 4681:CAMK1D 4676:CAMK1B 4671:CAMK1A 4525:PRKCB1 4462:PRKACA 4457:PRKACB 4452:PRKACG 4428:IKBKAP 4254:BCKDHB 4249:BCKDHA 4223:PRKAG3 4218:PRKAG2 4213:PRKAG1 4203:PRKAB2 4198:PRKAB1 4188:PRKAA2 4183:PRKAA1 4028:STK38L 3900:  3890:  3851:  3841:  3802:  3792:  3753:  3743:  3704:  3694:  3655:  3645:  3606:  3596:  3547:  3537:  3496:  3486:  3447:  3437:  3396:  3386:  3345:  3304:  3294:  3255:  3245:  3196:  3186:  3137:  3127:  3078:  3068:  3029:  2988:  2978:  2939:  2929:  2890:  2880:  2839:  2829:  2790:  2780:  2741:  2706:  2696:  2657:  2615:  2605:  2566:  2556:  2507:  2497:  2448:  2438:  2397:  2387:  2340:  2289:  2279:  2240:  2230:  2191:  2181:  2134:  2124:  2085:  2044:  2007:  1999:  1950:  1938:  1899:  1889:  1881:  1842:  1834:  1790:  1780:  1741:  1731:  1692:  1682:  1643:  1633:  1594:  1584:  1546:  1536:  1492:  1482:  1443:  1435:  1400:  1356:  1348:  1302:  1294:  1245:  1235:  1191:  1181:  1142:  1132:  1093:  1083:  1044:  1034:  995:  985:  938:Rictor 930:Rictor 925:Rictor 917:Rictor 913:Rictor 905:Rictor 688:serine 668:IGF-IR 655:, and 598:RICTOR 594:mTORC1 582:DEPTOR 551:mTORC2 505:q34.11 501:Chr. 9 484:Q9BPZ7 467:RefSeq 460:610558 420:Symbol 343:Q9BVC4 326:RefSeq 319:612190 279:Symbol 252:Chr. 5 230:RefSeq 211:253260 199:RICTOR 195:Symbol 184:RICTOR 135:Chr. 1 106:P42345 89:RefSeq 82:601231 34:Symbol 5971:Types 5727:MAP2K 5661:ACVR1 5654:BMPR2 5639:BMPR1 5564:GSK-3 5405:MAP3K 5366:MAPK9 5361:MAPK8 5339:MAPK7 5334:MAPK6 5329:MAPK4 5324:MAPK3 5319:MAPK1 5231:PFTK1 5226:PCTK3 5221:PCTK2 5216:PCTK1 5206:CDK12 5201:CDK10 5176:CDKL5 5156:CDKL2 5033:STK19 5028:EEF2K 5009:PHKG2 5004:PHKG1 4994:PHKA2 4989:PHKA1 4970:MYLK4 4965:MYLK3 4960:MYLK2 4936:DCLK1 4931:Titin 4921:TRIB3 4916:TRIB2 4911:TRIB1 4901:TSSK2 4881:STK40 4866:PSKH1 4861:PRKD3 4856:PRKD2 4836:PHKG2 4831:PHKG1 4821:OBSCN 4816:NUAK2 4811:NUAK1 4806:MKNK2 4801:MKNK1 4791:MARK4 4786:MARK3 4781:MARK2 4776:MARK1 4756:STK11 4751:DAPK3 4746:DAPK2 4741:DAPK1 4736:CHEK2 4731:CHEK1 4716:CAMK4 4691:CAMK2 4666:CAMK1 4661:BRSK2 4555:PRKCQ 4550:PRKCI 4545:PRKCG 4540:PRKCH 4535:PRKCE 4530:PRKCD 4491:PRKG1 4423:IKBKG 4418:IKBKE 4367:STK10 4362:FASTK 4288:IDH3G 4283:IDH3B 4278:IDH3A 4244:BCKDK 4038:ROCK1 4023:STK38 4018:MAST2 4013:MAST1 4008:LATS2 4003:LATS1 3517:eLife 2635:(PDF) 2005:S2CID 1840:S2CID 1441:S2CID 1354:S2CID 1300:S2CID 828:HDACs 800:Grb10 746:actin 686:at a 653:Cdc42 602:mSIN1 586:mLST8 496:Locus 448:18752 436:79109 364:p13.3 355:Locus 307:24825 295:64223 283:MLST8 268:MLST8 256:p13.1 247:Locus 223:28611 130:Locus 6063:list 6056:EC7 6050:list 6043:EC6 6037:list 6030:EC5 6024:list 6017:EC4 6011:list 6004:EC3 5998:list 5991:EC2 5985:list 5978:EC1 5554:TPK1 5530:CDC7 5488:MLKs 5481:KSR2 5476:KSR1 5471:BRAF 5466:ARAF 5461:RAFs 5196:CDK9 5191:CDK8 5186:CDK7 5181:CDK6 5171:CDK5 5166:CDK4 5161:CDK3 5151:CDK2 5146:CDK1 5127:PLK4 5122:PLK3 5117:PLK2 5112:PLK1 5067:PLK4 5062:PLK3 5057:PLK2 5052:PLK1 4999:PHKB 4955:MYLK 4926:TRIO 4896:SPEG 4891:SNRK 4851:PKD1 4846:PIM2 4841:PIM1 4826:PASK 4796:MELK 4726:CASK 4721:MLCK 4642:GRK6 4637:GRK5 4632:GRK4 4570:PKN3 4565:PKN2 4467:PRKY 4413:TBK1 4408:IKK2 4403:CHUK 4307:STK4 4273:IDH2 4158:PDK4 4153:PDK3 4148:PDK2 4143:PDK1 4122:WEE1 4117:Wee1 4085:mTOR 4073:AKT3 4068:AKT2 4063:AKT1 4053:SGK3 4048:SGK2 3898:PMID 3849:PMID 3800:PMID 3751:PMID 3702:PMID 3653:PMID 3604:PMID 3545:PMID 3494:PMID 3445:PMID 3394:PMID 3343:PMID 3302:PMID 3253:PMID 3194:PMID 3135:PMID 3076:PMID 3027:PMID 2986:PMID 2937:PMID 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Index

mTOR
MTOR
NCBI gene
2475
HGNC
3942
OMIM
601231
RefSeq
NM_004958
UniProt
P42345
EC number
2.7.11.1
Locus
Chr. 1
p36
Swiss-model
InterPro
RICTOR
RICTOR
NCBI gene
253260
HGNC
28611
RefSeq
NM_152756
Locus
Chr. 5
p13.1

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