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Non-receptor tyrosine kinase

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the binding of ATP and substrate to nRTKs, catalysis of phosphate transfer occurs in a cleft between these two lobes. It was found that nRTKs have some sequence preference around the target Tyr. For example, the Src preferred sequence is Glu–Glu/Asp–Ile–Tyr–Gly/Glu–Glu–Phe and Abl preferred sequence is Ile/Val–Tyr–Gly–Val–Leu/Val. Different preferred sequences around Tyr in Src and Abl suggest that these two types of nRTKs phosphorylates different targets. Non-receptor tyrosine kinases do not contain only a tyrosine kinase domain, nRTKs also possess domains that mediate protein-protein, protein-lipid, and protein-
570:(suppressor of cytokine signaling) proteins. These proteins contain a pseudo-substrate sequence thought to interfere with Jak substrate binding and phosphoryl transfer. In addition to a pseudo-substrate sequence, SOCS proteins possess an SH2 domain that binds to a phosphotyrosine in the Jak activation loop, which may facilitate interaction between the pseudosubstrate sequence and the kinase domain. Binding of the SH2 domain to the activation loop could also block substrate access directly or alter the conformation of the activation loop to repress catalytic activity. 563:, also lacking the pseudo-kinase domain, was able to mediate growth hormone signaling. The role of the pseudo-kinase domain in Jak regulation is still not fully understood. There are two tyrosine phosphorylation sites within the activation loop. It is known that the autophosphorylation of the first of these tyrosines is important for stimulation of tyrosine kinase activity and biological function, but the role of the second tyrosine is not clear. 4175: 25: 522:
second regulatory phosphorylation site in Src is Tyr-416. This is an autophosphorylation site in the activation loop. It was found that a phosphorylation of Tyr-416 and Tyr-416 can suppressing the transforming ability of the activating Tyr-527→Phe mutation by Tyr-416→Phe mutation leads to maximal stimulation of kinase activity.
443:) domains. The longer SH2 domain (~100 residues) binds phosphotyrosine (P-Tyr) residues in a sequence-specific manner. The P-Tyr interacts with SH domain in a deep cleft, which cannot bind unphosphorylated Tyr. The SH3 domain is smaller (~60 residues) and binds proline-containing sequences capable of forming a 492:
occurs via trans-autophosphorylation or phosphorylation by different nRTKs. It is possible to negatively regulate kinase activity by the phosphorylation of tyrosines outside of the activation loop. Protein tyrosine phosphatases (PTPs) restore nRTKs to their basal state of activity. In some cases PTPs
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sequences. One of the important domain of nRTKs is the tyrosine kinase catalytic domain, which is about 275 residues in length. The structure of the catalytic domain can be divided into a small and a large lobe, where ATP binds to the small lobe and the protein substrate binds to the large lobe. Upon
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and as a result of an carboxy-terminal truncation, v-Src lacks the negative regulatory site Tyr-527 leading this enzyme to be constitutively active that in turn causes uncontrolled growth of infected cells. Moreover, substitution of this tyrosine with phenylalanine in c-Src results in activation. A
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members possess a fully functional tyrosine kinase domain and additionally pseudo-kinase domain in which substitution of several key catalytic residues leads to inactivation of kinase activity. This pseudo-kinase domain is enzymatically nonfunctional, but maybe it plays a role in the regulation of
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contains SH3, SH2, and kinase domains in the same linear order as in Src, regulation of Abl is different. Abl lacks the negative regulatory phosphorylation site that is present in the carboxy terminus of Src, so the carboxy terminus of Abl does not have a functional role in the control of kinase
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activity. In a contrast to Src, mutations in the SH2 domain of Abl that abrogates phosphotyrosine binding do not activate Abl in vivo. For the repression of kinase activity of Abl is important the SH3 domain; mutations in the SH3 domain result in activation of Abl and cellular transformation.
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Van Etten RA, Debnath J, Zhou H, Casasnovas JM (May 1995). "Introduction of a loss-of-function point mutation from the SH3 region of the Caenorhabditis elegans sem-5 gene activates the transforming ability of c-abl in vivo and abolishes binding of proline-rich ligands in vitro".
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The mutation in a gene for non-receptor tyrosine kinase can results an aberrant activity of this enzyme. This pathologically increased activity of nRTK may be responsible for growth and progression of cancer cells, the induction of drug-resistance, formation of
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can be increased by phosphorylation of Tyr-493 in the activation loop by Src family member Lck. Conversely the phosphorylation of Tyr-492 inhibit the kinase activity of Zap70; the mutation of Tyr-492 to phenylalanine results in Zap70 hyperactivity.
543:(immunoreceptor tyrosine-based activation motif) sequences in the zeta chain of the T-cell receptor is thought to relieve an inhibitory restraint on the kinase domain, leading to stimulation of catalytic activity. Kinase activity of 475:
lipids that have been phosphorylated at particular positions on the head group. These enzymes can bind to activated signaling complexes at the membrane through PH domain interactions with phosphorylated phosphatidylinositol lipids.
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Tsukada S, Saffran DC, Rawlings DJ, Parolini O, Allen RC, Klisak I, Sparkes RS, Kubagawa H, Mohandas T, Quan S (January 1993). "Deficient expression of a B cell cytoplasmic tyrosine kinase in human X-linked agammaglobulinemia".
559:, in which the pseudo-kinase domain is deleted, showed that these mutant enzyme lacks catalytic activity in vitro and is not capable of interferon-mediated signal transduction. In contrast, another mutant of the Jak family 1059:
Songyang Z, Carraway KL, Eck MJ, Harrison SC, Feldman RA, Mohammadi M, Schlessinger J, Hubbard SR, Smith DP, Eng C (February 1995). "Catalytic specificity of protein-tyrosine kinases is critical for selective signalling".
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Both the SH2 and SH3 domains are important for a negative regulation of Src activity. Mutations in the SH2 and SH3 domains that disrupt binding of phosphotyrosine lead to activation of kinase activity. Although the nRTK
2873: 447:. Some nRTKs without SH2 and SH3 domains possess some subfamily-specific domains used for protein-protein interactions. For example, specific domains that target enzymes to the cytoplasmic part of cytokine receptors ( 595:
are used for the targeted blockade of RTK, which block the extracellular domain of the receptor and prevent the binding of a ligand. For the specific blockade of nRTKs, however, low molecular weight substances called
296:, enzymes that can transfer the phosphate group from ATP to a tyrosine residue of a protein (phosphorylation). These enzymes regulate many cellular functions by switching on or switching off other enzymes in a cell. 1244:
Nada S, Okada M, MacAuley A, Cooper JA, Nakagawa H (May 1991). "Cloning of a complementary DNA for a protein-tyrosine kinase that specifically phosphorylates a negative regulatory site of p60c-src".
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tail. There are two important regulatory tyrosine phosphorylation sites. To repress kinase activity it is possible by phosphorylation of Tyr-527 in the carboxy-terminal tail of Src by the nRTK
1839: 303:(RTKs), the second subgroup of tyrosine kinases, the non-receptor tyrosine kinases are cytosolic enzymes. Thirty-two non-receptor tyrosine kinases have been identified in human cells ( 1832: 394:
is involved in signaling mediated by B-cell receptor. Lyn is activated by stimulation of B-cell receptor, which leads to the recruitment and phosphorylation of Zap70-related nRTK,
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Kmiecik TE, Shalloway D (April 1987). "Activation and suppression of pp60c-src transforming ability by mutation of its primary sites of tyrosine phosphorylation".
540: 3320: 1855: 244: 1782:"Cytokine-inducible SH2 protein-3 (CIS3/SOCS3) inhibits Janus tyrosine kinase by binding through the N-terminal kinase inhibitory region as well as SH2 domain" 517:. By the experiment of v-Src, an oncogenic variant of Src, the importance of this phosphorylation site was confirmed. This oncogenic v-Src is a product of the 459:-binding domain (Fak family). The nRTK Abl possess the SH2 and SH3 domains, but also possesses other domains for interactions: F actin–binding domain and a 3744: 2905: 509:
terminus, a region of positively charged residues, a short region with low sequence homology, SH3 and SH2 domains, a tyrosine kinase domain, and a short
1898: 2343: 1386:"Mutational analysis of the Src SH3 domain: the same residues of the ligand binding surface are important for intra- and intermolecular interactions" 467:
and is found in both the nucleus and the cytoplasm. In addition to SH2 and SH3 domains, Btk/Tec subfamily of nRTKs possess another modular domain, a
3617: 2850: 2486: 2394: 2291: 662: 2005: 1961: 3043: 2808: 1512:"Syk is activated by phosphotyrosine-containing peptides representing the tyrosine-based activation motifs of the high affinity receptor for IgE" 591:
blocks intracellular processes involved in the tumor transformation of cells and / or maintenance of malignant phenotype of tumor cells. Usually
587:. The inhibition of nRTKs could help to a treatment of these tumors. Some of nRTKs inhibitors are already tested as an anti-cancer agents. This 3358: 1888: 3000: 3028: 2787: 2710: 1602:"Two novel protein-tyrosine kinases, each with a second phosphotransferase-related catalytic domain, define a new class of protein kinase" 4200: 3396: 3387: 3087: 3082: 3077: 3072: 484:
The most common theme in nRTKs and RTK regulation is tyrosine phosphorylation. With few exceptions, phosphorylation of tyrosines in the
3281: 3272: 2830: 3894: 3063: 2239: 61: 1148:"Identification and analysis of PH domain-containing targets of phosphatidylinositol 3-kinase using a novel in vivo assay in yeast" 913:
Vihinen M, Vetrie D, Maniar HS, Ochs HD, Zhu Q, VorechovskĂ˝ I, Webster AD, Notarangelo LD, Nilsson L, Sowadski JM (December 1994).
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Cooper JA, Gould KL, Cartwright CA, Hunter T (March 1986). "Tyr527 is phosphorylated in pp60c-src: implications for regulation".
237: 2742: 1651:"Distinct domains of the protein tyrosine kinase tyk2 required for binding of interferon-alpha/beta and for signal transduction" 386:, binds to this T-cell receptor and then participates in downstream signaling events that mediate transcriptional activation of 2898: 2798: 2000: 1976: 1956: 422:-spanning region. Most of the nRTKs are localized in the cytoplasm, but some nRTKs are anchored to the cell membrane through 188: 164: 4050: 2605: 1553:"Distinct tyrosine phosphorylation sites in ZAP-70 mediate activation and negative regulation of antigen receptor function" 600:(TKIs) are used, that block the transduction cascade either at the intracytosplasmatic level, or directly block the nRTKs. 3111: 2557: 2010: 539:
The kinase activity of Syk is regulated by the SH2 domains. Binding of the two SH2 domains to the tyrosine-phosphorylated
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Starr R, Novak U, Willson TA, Inglese M, Murphy V, Alexander WS, Metcalf D, Nicola NA, Hilton DJ, Ernst M (August 1997).
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Isakoff SJ, Cardozo T, Andreev J, Li Z, Ferguson KM, Abagyan R, Lemmon MA, Aronheim A, Skolnik EY (September 1998).
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Sasaki A, Yasukawa H, Suzuki A, Kamizono S, Syoda T, Kinjyo I, Sasaki M, Johnston JA, Yoshimura A (June 1999).
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modification. These enzymes commonly have a modular construction and individual domains are joined together by
402:, is also involved in signaling mediated by the B-cell receptor. Mutations in the Btk gene are responsible for 310:). Non-receptor tyrosine kinases regulate cell growth, proliferation, differentiation, adhesion, migration and 304: 87: 169: 3947: 3660: 3651: 2638: 2348: 2318: 2303: 2266: 693: 687: 351: 281: 2949: 1926: 285: 249: 3968: 3887: 3612: 3296: 2719: 2530: 2298: 657: 651: 592: 514: 157: 4040: 1692:"Activation of Jak2 catalytic activity requires phosphorylation of Y1007 in the kinase activation loop" 2122: 1304: 1253: 1069: 926: 472: 338:
in the immune system. Signaling by many receptors is dependent on nRTKs including T-cell receptors (
4004: 3310: 2701: 2574: 327: 185: 109: 4195: 3937: 3694: 3684: 3675: 3503: 3494: 2107: 2072: 1811: 1435:"Mutagenic analysis of the roles of SH2 and SH3 domains in regulation of the Abl tyrosine kinase" 1366: 1277: 1226: 1093: 1041: 998: 895: 721: 711: 705: 584: 518: 460: 355: 2883: 1824: 378:. When antigen binds to T-cell receptor, Lck becomes autophosphorylated and phosphorylates the 3728: 1995: 1951: 1803: 1762: 1721: 1672: 1631: 1582: 1533: 1492: 1464: 1415: 1358: 1320: 1269: 1218: 1177: 1128: 1085: 1033: 1016:
Neet K, Hunter T (February 1996). "Vertebrate non-receptor protein-tyrosine kinase families".
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interactions. One of the protein-protein interaction domains in nRTKs are the Src homology 2 (
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Unlike receptor tyrosine kinases, nRTKs lack receptor-like features such as an extracellular
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Kuriyan J, Cowburn D (1997). "Modular peptide recognition domains in eukaryotic signaling".
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Weiss A, Littman DR (January 1994). "Signal transduction by lymphocyte antigen receptors".
145: 4030: 4014: 3927: 3593: 3262: 3247: 3237: 3232: 3212: 3207: 3202: 3197: 3192: 3183: 2918: 2686: 2681: 2442: 2437: 2413: 2408: 2374: 2271: 2199: 2023: 644: 489: 485: 427: 343: 339: 293: 121: 1308: 1257: 1073: 930: 915:"Structural basis for chromosome X-linked agammaglobulinemia: a tyrosine kinase disease" 92: 4179: 4068: 4009: 3723: 3718: 3713: 3097: 2914: 2385: 1551:
Kong G, Dalton M, Bubeck Wardenburg J, Straus D, Kurosaki T, Chan AC (September 1996).
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Velazquez L, Mogensen KE, Barbieri G, Fellous M, Uzé G, Pellegrini S (February 1995).
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Wilks AF, Harpur AG, Kurban RR, Ralph SJ, ZĂĽrcher G, Ziemiecki A (April 1991).
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Feng J, Witthuhn BA, Matsuda T, Kohlhuber F, Kerr IM, Ihle JN (May 1997).
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Jak activity. The experiments with a mutant of the Jak family member
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of nRTKs leads to an increase in enzymatic activity. Activation loop
415: 335: 331: 273: 232: 128: 116: 104: 1197:"From form to function: signaling by protein tyrosine phosphatases" 4107: 3641: 3519: 3484: 3479: 3455: 3257: 3242: 3227: 3222: 3217: 3169: 3164: 3140: 3135: 3126: 3038: 3033: 3010: 2981: 2976: 2658: 2653: 2615: 2600: 2567: 2562: 2523: 2518: 2506: 2501: 2496: 2491: 2479: 2457: 2452: 2447: 2224: 2219: 2214: 2209: 2169: 2164: 2102: 2097: 2092: 2087: 2062: 2057: 2052: 2047: 2042: 2037: 2032: 680: 544: 383: 379: 292:. Non-receptor tyrosine kinases are a subgroup of protein family 3759: 3689: 3636: 3627: 3588: 3579: 3569: 3450: 3441: 3431: 3377: 3368: 3353: 3344: 3334: 3329: 3305: 3106: 2958: 2840: 2825: 2610: 2550: 2545: 2540: 2535: 2474: 2469: 2313: 2286: 2281: 2194: 2189: 2184: 2179: 2174: 2151: 2146: 2141: 2136: 2131: 2082: 2077: 2067: 777: 716: 675: 669: 639: 633: 623: 567: 560: 140: 3876: 3540: 2934: 2887: 1828: 3790: 3785: 3780: 3754: 810: 804: 797: 792: 787: 772: 432: 395: 391: 375: 363: 359: 18: 2874:
deficiencies of intracellular signaling peptides and proteins
314:, and they are critical components in the regulation of the 3872: 406:, a disease characterized by the lack of mature B-cells. 1384:
Erpel T, Superti-Furga G, Courtneidge SA (March 1995).
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that is responsible for catalysing the transfer of a
4059: 4023: 3992: 3961: 3910: 3838: 3799: 3768: 3737: 3703: 3674: 3650: 3626: 3602: 3578: 3554: 3512: 3493: 3464: 3440: 3424: 3405: 3386: 3367: 3343: 3319: 3295: 3271: 3182: 3149: 3125: 3096: 3062: 3019: 2990: 2957: 2948: 2818: 2797: 2776: 2756: 2728: 2709: 2699: 2674: 2631: 2590: 2393: 2383: 2362: 2336: 2257: 1975: 1925: 1916: 1907: 1881: 1862: 608:Examples of non-receptor tyrosine kinases include: 326:The main function of nRTKs is their involvement in 243: 231: 219: 214: 194: 175: 163: 151: 139: 127: 115: 103: 98: 86: 81: 76: 34:
may be too technical for most readers to understand
2748:Sh2 domain-containing protein tyrosine phosphatase 1336: 1334: 3888: 2899: 1856:Intracellular signaling peptides and proteins 1840: 8: 3895: 3881: 3873: 3551: 3537: 2954: 2945: 2931: 2906: 2892: 2884: 2743:Receptor-like protein tyrosine phosphatase 2706: 2390: 1922: 1913: 1847: 1833: 1825: 1510:Shiue L, Zoller MJ, Brugge JS (May 1995). 211: 2344:Cyclin-dependent kinase inhibitor protein 1797: 1756: 1715: 1666: 1625: 1576: 1527: 1458: 1409: 1212: 1171: 948: 938: 62:Learn how and when to remove this message 46:, without removing the technical details. 2851:Phosphatidylethanolamine binding protein 2487:Interleukin-1 receptor associated kinase 1899:Ca2+/calmodulin-dependent protein kinase 4170: 862: 2606:Focal adhesion protein-tyrosine kinase 1889:Intracellular calcium-sensing proteins 73: 44:make it understandable to non-experts 7: 505:contain the same typical structure: 493:positively regulate nRTKs activity. 1195:Tonks NK, Neel BG (November 1996). 2831:Signal transducing adaptor protein 2006:3',5'-cyclic-GMP phosphodiesterase 1962:3',5'-cyclic-AMP phosphodiesterase 1433:Mayer BJ, Baltimore D (May 1994). 1402:10.1002/j.1460-2075.1995.tb07077.x 1030:10.1046/j.1365-2443.1996.d01-234.x 14: 2826:Activating transcription factor 6 2240:G protein-coupled receptor kinase 390:genes. Another Src family member 380:zeta chain of the T-cell receptor 350:), Ig receptors, erythropoietin ( 4173: 2370:Phosphoinositide phospholipase C 1799:10.1046/j.1365-2443.1999.00263.x 1125:10.1146/annurev.biophys.26.1.259 370:require for their signaling the 23: 469:pleckstrin homology (PH) domain 2809:GTP-binding protein regulators 2799:GTP-binding protein regulators 1113:Annu Rev Biophys Biomol Struct 1: 3543:Non-receptor tyrosine kinases 2558:Rho-associated protein kinase 1214:10.1016/S0092-8674(00)81357-4 382:, subsequently another nRTK, 2764:Dual-specificity phosphatase 2739:protein tyrosine phosphatase 2245:AMP-activated protein kinase 1355:10.1016/0092-8674(87)90756-2 987:10.1016/0092-8674(93)90667-F 919:Proc. Natl. Acad. Sci. U.S.A 884:10.1016/0092-8674(94)90334-4 263:non-receptor tyrosine kinase 77:Non-receptor tyrosine kinase 2788:apoptosis signaling pathway 566:JAKs are also regulated by 471:. These PH domains bind to 465:nuclear localization signal 404:X-linked agammaglobulinemia 4217: 4201:Enzymes of known structure 288:, to tyrosine residues in 4051:Michaelis–Menten kinetics 3550: 3536: 2944: 2937:Receptor tyrosine kinases 2930: 2869: 2632:Serine/threonine/tyrosine 2235: 2118: 2019: 598:Tyrosine-kinase inhibitor 445:polyproline type II helix 301:receptor tyrosine kinases 210: 3943:Diffusion-limited enzyme 2846:Olfactory marker protein 2433:Glycogen synthase kinase 1936:Heterotrimeric G protein 1758:10.1074/jbc.272.32.19982 1529:10.1074/jbc.270.18.10498 1164:10.1093/emboj/17.18.5374 940:10.1073/pnas.91.26.12803 2950:Growth factor receptors 2639:Dual-specificity kinase 2349:Cyclin-dependent kinase 1317:10.1126/science.2420005 282:nucleoside triphosphate 16:Class of kinase enzymes 1668:10.1074/jbc.270.7.3327 455:-binding domain and a 418:-binding domain and a 4036:Eadie–Hofstee diagram 3969:Allosteric regulation 2720:Protein phosphatase 2 2531:p21-activated kinases 1708:10.1128/mcb.17.5.2497 1618:10.1128/MCB.11.4.2057 1569:10.1128/MCB.16.9.5026 1451:10.1128/mcb.14.5.2883 593:monoclonal antibodies 451:) or two domains: an 342:), B-cell receptors ( 4046:Lineweaver–Burk plot 3021:PDGF receptor family 2123:G beta-gamma complex 501:Tyrosine kinases of 473:phosphatidylinositol 3425:ROS receptor family 2959:EGF receptor family 2702:protein phosphatase 2575:Ribosomal s6 kinase 1309:1986Sci...231.1431C 1258:1991Natur.351...69N 1074:1995Natur.373..536S 931:1994PNAS...9112803V 356:prolactin receptors 346:), IL-2 receptors ( 328:signal transduction 4005:Enzyme superfamily 3938:Enzyme promiscuity 1872:MAP kinase pathway 585:neovascularization 535:ZAP70/Syk and JAKs 519:Rous sarcoma virus 461:DNA-binding domain 4161: 4160: 3870: 3869: 3866: 3865: 3862: 3861: 3532: 3531: 3528: 3527: 3178: 3177: 2881: 2880: 2836:I-kappa B protein 2772: 2771: 2695: 2694: 2332: 2331: 2253: 2252: 1996:Guanylate cyclase 1952:Adenylate cyclase 1522:(18): 10498–502. 259: 258: 255: 254: 158:metabolic pathway 72: 71: 64: 4208: 4178: 4177: 4169: 4041:Hanes–Woolf plot 3984:Enzyme activator 3979:Enzyme inhibitor 3953:Enzyme catalysis 3897: 3890: 3883: 3874: 3552: 3538: 2992:Insulin receptor 2955: 2946: 2932: 2919:tyrosine kinases 2908: 2901: 2894: 2885: 2711:Serine/threonine 2707: 2395:Serine/threonine 2391: 2011:Protein kinase G 1967:Protein kinase A 1923: 1914: 1849: 1842: 1835: 1826: 1820: 1819: 1801: 1777: 1771: 1770: 1760: 1736: 1730: 1729: 1719: 1687: 1681: 1680: 1670: 1646: 1640: 1639: 1629: 1597: 1591: 1590: 1580: 1548: 1542: 1541: 1531: 1507: 1501: 1500: 1479: 1473: 1472: 1462: 1430: 1424: 1423: 1413: 1381: 1375: 1374: 1338: 1329: 1328: 1303:(4744): 1431–4. 1292: 1286: 1285: 1266:10.1038/351069a0 1241: 1235: 1234: 1216: 1192: 1186: 1185: 1175: 1143: 1137: 1136: 1108: 1102: 1101: 1082:10.1038/373536a0 1056: 1050: 1049: 1013: 1007: 1006: 969: 963: 962: 952: 942: 910: 904: 903: 867: 589:targeted therapy 511:carboxy-terminal 398:. Another nRTK, 294:tyrosine kinases 212: 74: 67: 60: 56: 53: 47: 27: 26: 19: 4216: 4215: 4211: 4210: 4209: 4207: 4206: 4205: 4186: 4185: 4184: 4172: 4164: 4162: 4157: 4069:Oxidoreductases 4055: 4031:Enzyme kinetics 4019: 4015:List of enzymes 3988: 3957: 3928:Catalytic triad 3906: 3901: 3871: 3858: 3834: 3795: 3764: 3733: 3699: 3670: 3646: 3622: 3598: 3574: 3546: 3524: 3508: 3489: 3460: 3436: 3420: 3401: 3382: 3363: 3339: 3315: 3291: 3267: 3174: 3145: 3121: 3092: 3058: 3015: 2986: 2940: 2926: 2915:Protein kinases 2912: 2882: 2877: 2865: 2814: 2793: 2768: 2752: 2724: 2691: 2682:Arginine kinase 2670: 2627: 2586: 2379: 2375:Phospholipase C 2358: 2328: 2249: 2231: 2161: 2128: 2114: 2029: 2024:G alpha subunit 2015: 1971: 1903: 1877: 1858: 1853: 1823: 1779: 1778: 1774: 1751:(32): 19982–6. 1738: 1737: 1733: 1702:(5): 2497–501. 1696:Mol. Cell. Biol 1689: 1688: 1684: 1648: 1647: 1643: 1606:Mol. Cell. Biol 1599: 1598: 1594: 1557:Mol. Cell. Biol 1550: 1549: 1545: 1509: 1508: 1504: 1491:(10): 1977–88. 1481: 1480: 1476: 1439:Mol. Cell. Biol 1432: 1431: 1427: 1383: 1382: 1378: 1340: 1339: 1332: 1294: 1293: 1289: 1252:(6321): 69–72. 1243: 1242: 1238: 1194: 1193: 1189: 1158:(18): 5374–87. 1145: 1144: 1140: 1110: 1109: 1105: 1068:(6514): 536–9. 1058: 1057: 1053: 1015: 1014: 1010: 971: 970: 966: 925:(26): 12803–7. 912: 911: 907: 869: 868: 864: 860: 855: 606: 576: 537: 499: 490:phosphorylation 486:activation loop 482: 428:flexible linker 412: 324: 284:donor, such as 68: 57: 51: 48: 40:help improve it 37: 28: 24: 17: 12: 11: 5: 4214: 4212: 4204: 4203: 4198: 4188: 4187: 4183: 4182: 4159: 4158: 4156: 4155: 4142: 4129: 4116: 4103: 4090: 4077: 4063: 4061: 4057: 4056: 4054: 4053: 4048: 4043: 4038: 4033: 4027: 4025: 4021: 4020: 4018: 4017: 4012: 4007: 4002: 3996: 3994: 3993:Classification 3990: 3989: 3987: 3986: 3981: 3976: 3971: 3965: 3963: 3959: 3958: 3956: 3955: 3950: 3945: 3940: 3935: 3930: 3925: 3920: 3914: 3912: 3908: 3907: 3902: 3900: 3899: 3892: 3885: 3877: 3868: 3867: 3864: 3863: 3860: 3859: 3857: 3856: 3851: 3845: 3843: 3836: 3835: 3833: 3832: 3827: 3822: 3817: 3812: 3806: 3804: 3797: 3796: 3794: 3793: 3788: 3783: 3778: 3772: 3770: 3766: 3765: 3763: 3762: 3757: 3752: 3747: 3741: 3739: 3735: 3734: 3732: 3731: 3726: 3721: 3716: 3710: 3708: 3701: 3700: 3698: 3697: 3692: 3687: 3681: 3679: 3672: 3671: 3669: 3668: 3663: 3657: 3655: 3648: 3647: 3645: 3644: 3639: 3633: 3631: 3624: 3623: 3621: 3620: 3615: 3609: 3607: 3600: 3599: 3597: 3596: 3591: 3585: 3583: 3576: 3575: 3573: 3572: 3567: 3561: 3559: 3548: 3547: 3541: 3534: 3533: 3530: 3529: 3526: 3525: 3523: 3522: 3516: 3514: 3510: 3509: 3507: 3506: 3500: 3498: 3491: 3490: 3488: 3487: 3482: 3477: 3471: 3469: 3462: 3461: 3459: 3458: 3453: 3447: 3445: 3442:AATYK receptor 3438: 3437: 3435: 3434: 3428: 3426: 3422: 3421: 3419: 3418: 3412: 3410: 3403: 3402: 3400: 3399: 3393: 3391: 3384: 3383: 3381: 3380: 3374: 3372: 3365: 3364: 3362: 3361: 3356: 3350: 3348: 3341: 3340: 3338: 3337: 3332: 3326: 3324: 3317: 3316: 3314: 3313: 3308: 3302: 3300: 3293: 3292: 3290: 3289: 3284: 3278: 3276: 3269: 3268: 3266: 3265: 3260: 3255: 3250: 3245: 3240: 3235: 3230: 3225: 3220: 3215: 3210: 3205: 3200: 3195: 3189: 3187: 3180: 3179: 3176: 3175: 3173: 3172: 3167: 3162: 3156: 3154: 3147: 3146: 3144: 3143: 3138: 3132: 3130: 3123: 3122: 3120: 3119: 3114: 3109: 3103: 3101: 3098:VEGF receptors 3094: 3093: 3091: 3090: 3085: 3080: 3075: 3069: 3067: 3060: 3059: 3057: 3056: 3050: 3041: 3036: 3031: 3025: 3023: 3017: 3016: 3014: 3013: 3008: 3003: 2997: 2995: 2988: 2987: 2985: 2984: 2979: 2974: 2969: 2963: 2961: 2952: 2942: 2941: 2935: 2928: 2927: 2913: 2911: 2910: 2903: 2896: 2888: 2879: 2878: 2870: 2867: 2866: 2864: 2863: 2858: 2853: 2848: 2843: 2838: 2833: 2828: 2822: 2820: 2816: 2815: 2813: 2812: 2803: 2801: 2795: 2794: 2792: 2791: 2782: 2780: 2774: 2773: 2770: 2769: 2767: 2766: 2760: 2758: 2754: 2753: 2751: 2750: 2745: 2735: 2733: 2726: 2725: 2723: 2722: 2716: 2714: 2704: 2697: 2696: 2693: 2692: 2690: 2689: 2684: 2678: 2676: 2672: 2671: 2669: 2668: 2667: 2666: 2661: 2656: 2651: 2646: 2635: 2633: 2629: 2628: 2626: 2625: 2620: 2619: 2618: 2613: 2603: 2597: 2595: 2588: 2587: 2585: 2584: 2583: 2582: 2572: 2571: 2570: 2565: 2555: 2554: 2553: 2548: 2543: 2538: 2528: 2527: 2526: 2521: 2511: 2510: 2509: 2504: 2499: 2494: 2484: 2483: 2482: 2477: 2472: 2462: 2461: 2460: 2455: 2450: 2445: 2440: 2430: 2429: 2428: 2418: 2417: 2416: 2411: 2400: 2398: 2388: 2386:protein kinase 2381: 2380: 2378: 2377: 2372: 2366: 2364: 2360: 2359: 2357: 2356: 2351: 2346: 2340: 2338: 2334: 2333: 2330: 2329: 2327: 2326: 2321: 2316: 2311: 2306: 2301: 2296: 2295: 2294: 2289: 2284: 2274: 2269: 2263: 2261: 2255: 2254: 2251: 2250: 2248: 2247: 2242: 2236: 2233: 2232: 2230: 2229: 2228: 2227: 2222: 2217: 2212: 2207: 2202: 2197: 2192: 2187: 2182: 2177: 2172: 2167: 2159: 2156: 2155: 2154: 2149: 2144: 2139: 2134: 2126: 2119: 2116: 2115: 2113: 2112: 2111: 2110: 2105: 2100: 2095: 2090: 2085: 2080: 2075: 2070: 2065: 2060: 2055: 2050: 2045: 2040: 2035: 2027: 2020: 2017: 2016: 2014: 2013: 2008: 2003: 1998: 1993: 1988: 1982: 1980: 1973: 1972: 1970: 1969: 1964: 1959: 1954: 1949: 1948: 1947: 1932: 1930: 1920: 1918:Heterotrimeric 1911: 1905: 1904: 1902: 1901: 1896: 1891: 1885: 1883: 1879: 1878: 1876: 1875: 1866: 1864: 1860: 1859: 1854: 1852: 1851: 1844: 1837: 1829: 1822: 1821: 1772: 1731: 1682: 1661:(7): 3327–34. 1641: 1612:(4): 2057–65. 1592: 1563:(9): 5026–35. 1543: 1502: 1474: 1445:(5): 2883–94. 1425: 1376: 1330: 1287: 1236: 1187: 1138: 1103: 1051: 1008: 964: 905: 861: 859: 856: 854: 853: 852: 851: 846: 841: 836: 831: 820: 819: 818: 813: 802: 801: 800: 795: 790: 785: 780: 775: 770: 765: 754: 753: 752: 747: 742: 737: 726: 725: 724: 719: 714: 703: 702: 701: 696: 685: 684: 683: 678: 667: 666: 665: 660: 649: 648: 647: 642: 630: 629: 628: 627: 626: 621: 605: 602: 575: 572: 536: 533: 498: 495: 481: 478: 457:focal adhesion 424:amino-terminal 411: 408: 374:family member 323: 320: 257: 256: 253: 252: 247: 241: 240: 235: 229: 228: 223: 217: 216: 208: 207: 198: 192: 191: 180: 173: 172: 167: 161: 160: 155: 149: 148: 143: 137: 136: 131: 125: 124: 119: 113: 112: 107: 101: 100: 96: 95: 90: 84: 83: 79: 78: 70: 69: 31: 29: 22: 15: 13: 10: 9: 6: 4: 3: 2: 4213: 4202: 4199: 4197: 4194: 4193: 4191: 4181: 4176: 4171: 4167: 4153: 4149: 4148: 4143: 4140: 4136: 4135: 4130: 4127: 4123: 4122: 4117: 4114: 4110: 4109: 4104: 4101: 4097: 4096: 4091: 4088: 4084: 4083: 4078: 4075: 4071: 4070: 4065: 4064: 4062: 4058: 4052: 4049: 4047: 4044: 4042: 4039: 4037: 4034: 4032: 4029: 4028: 4026: 4022: 4016: 4013: 4011: 4010:Enzyme family 4008: 4006: 4003: 4001: 3998: 3997: 3995: 3991: 3985: 3982: 3980: 3977: 3975: 3974:Cooperativity 3972: 3970: 3967: 3966: 3964: 3960: 3954: 3951: 3949: 3946: 3944: 3941: 3939: 3936: 3934: 3933:Oxyanion hole 3931: 3929: 3926: 3924: 3921: 3919: 3916: 3915: 3913: 3909: 3905: 3898: 3893: 3891: 3886: 3884: 3879: 3878: 3875: 3855: 3852: 3850: 3847: 3846: 3844: 3841: 3837: 3831: 3828: 3826: 3823: 3821: 3818: 3816: 3813: 3811: 3808: 3807: 3805: 3802: 3798: 3792: 3789: 3787: 3784: 3782: 3779: 3777: 3774: 3773: 3771: 3767: 3761: 3758: 3756: 3753: 3751: 3748: 3746: 3743: 3742: 3740: 3736: 3730: 3727: 3725: 3722: 3720: 3717: 3715: 3712: 3711: 3709: 3706: 3702: 3696: 3693: 3691: 3688: 3686: 3683: 3682: 3680: 3677: 3673: 3667: 3664: 3662: 3659: 3658: 3656: 3653: 3649: 3643: 3640: 3638: 3635: 3634: 3632: 3629: 3625: 3619: 3616: 3614: 3611: 3610: 3608: 3605: 3601: 3595: 3592: 3590: 3587: 3586: 3584: 3581: 3577: 3571: 3568: 3566: 3563: 3562: 3560: 3557: 3553: 3549: 3545:(EC 2.7.10.2) 3544: 3539: 3535: 3521: 3518: 3517: 3515: 3513:uncategorised 3511: 3505: 3502: 3501: 3499: 3496: 3492: 3486: 3483: 3481: 3478: 3476: 3473: 3472: 3470: 3467: 3463: 3457: 3454: 3452: 3449: 3448: 3446: 3443: 3439: 3433: 3430: 3429: 3427: 3423: 3417: 3414: 3413: 3411: 3408: 3407:MuSK receptor 3404: 3398: 3395: 3394: 3392: 3389: 3385: 3379: 3376: 3375: 3373: 3370: 3369:PTK7 receptor 3366: 3360: 3357: 3355: 3352: 3351: 3349: 3346: 3342: 3336: 3333: 3331: 3328: 3327: 3325: 3322: 3318: 3312: 3309: 3307: 3304: 3303: 3301: 3298: 3294: 3288: 3285: 3283: 3280: 3279: 3277: 3274: 3270: 3264: 3261: 3259: 3256: 3254: 3251: 3249: 3246: 3244: 3241: 3239: 3236: 3234: 3231: 3229: 3226: 3224: 3221: 3219: 3216: 3214: 3211: 3209: 3206: 3204: 3201: 3199: 3196: 3194: 3191: 3190: 3188: 3185: 3181: 3171: 3168: 3166: 3163: 3161: 3158: 3157: 3155: 3152: 3148: 3142: 3139: 3137: 3134: 3133: 3131: 3128: 3124: 3118: 3115: 3113: 3110: 3108: 3105: 3104: 3102: 3099: 3095: 3089: 3086: 3084: 3081: 3079: 3076: 3074: 3071: 3070: 3068: 3065: 3061: 3054: 3051: 3049: 3045: 3042: 3040: 3037: 3035: 3032: 3030: 3027: 3026: 3024: 3022: 3018: 3012: 3009: 3007: 3004: 3002: 2999: 2998: 2996: 2993: 2989: 2983: 2980: 2978: 2975: 2973: 2970: 2968: 2965: 2964: 2962: 2960: 2956: 2953: 2951: 2947: 2943: 2939:(EC 2.7.10.1) 2938: 2933: 2929: 2924: 2920: 2916: 2909: 2904: 2902: 2897: 2895: 2890: 2889: 2886: 2876: 2875: 2868: 2862: 2859: 2857: 2854: 2852: 2849: 2847: 2844: 2842: 2839: 2837: 2834: 2832: 2829: 2827: 2824: 2823: 2821: 2817: 2811: 2810: 2805: 2804: 2802: 2800: 2796: 2790: 2789: 2784: 2783: 2781: 2779: 2775: 2765: 2762: 2761: 2759: 2755: 2749: 2746: 2744: 2740: 2737: 2736: 2734: 2731: 2727: 2721: 2718: 2717: 2715: 2712: 2708: 2705: 2703: 2698: 2688: 2685: 2683: 2680: 2679: 2677: 2673: 2665: 2662: 2660: 2657: 2655: 2652: 2650: 2647: 2645: 2642: 2641: 2640: 2637: 2636: 2634: 2630: 2624: 2621: 2617: 2614: 2612: 2609: 2608: 2607: 2604: 2602: 2599: 2598: 2596: 2593: 2589: 2581: 2578: 2577: 2576: 2573: 2569: 2566: 2564: 2561: 2560: 2559: 2556: 2552: 2549: 2547: 2544: 2542: 2539: 2537: 2534: 2533: 2532: 2529: 2525: 2522: 2520: 2517: 2516: 2515: 2512: 2508: 2505: 2503: 2500: 2498: 2495: 2493: 2490: 2489: 2488: 2485: 2481: 2478: 2476: 2473: 2471: 2468: 2467: 2466: 2463: 2459: 2456: 2454: 2451: 2449: 2446: 2444: 2441: 2439: 2436: 2435: 2434: 2431: 2427: 2424: 2423: 2422: 2419: 2415: 2412: 2410: 2407: 2406: 2405: 2404:Casein kinase 2402: 2401: 2399: 2396: 2392: 2389: 2387: 2382: 2376: 2373: 2371: 2368: 2367: 2365: 2361: 2355: 2352: 2350: 2347: 2345: 2342: 2341: 2339: 2335: 2325: 2322: 2320: 2317: 2315: 2312: 2310: 2307: 2305: 2302: 2300: 2297: 2293: 2290: 2288: 2285: 2283: 2280: 2279: 2278: 2275: 2273: 2270: 2268: 2265: 2264: 2262: 2260: 2256: 2246: 2243: 2241: 2238: 2237: 2234: 2226: 2223: 2221: 2218: 2216: 2213: 2211: 2208: 2206: 2203: 2201: 2198: 2196: 2193: 2191: 2188: 2186: 2183: 2181: 2178: 2176: 2173: 2171: 2168: 2166: 2163: 2162: 2157: 2153: 2150: 2148: 2145: 2143: 2140: 2138: 2135: 2133: 2130: 2129: 2124: 2121: 2120: 2117: 2109: 2106: 2104: 2101: 2099: 2096: 2094: 2091: 2089: 2086: 2084: 2081: 2079: 2076: 2074: 2071: 2069: 2066: 2064: 2061: 2059: 2056: 2054: 2051: 2049: 2046: 2044: 2041: 2039: 2036: 2034: 2031: 2030: 2025: 2022: 2021: 2018: 2012: 2009: 2007: 2004: 2002: 1999: 1997: 1994: 1992: 1989: 1987: 1984: 1983: 1981: 1978: 1974: 1968: 1965: 1963: 1960: 1958: 1955: 1953: 1950: 1946: 1942: 1939: 1938: 1937: 1934: 1933: 1931: 1928: 1924: 1921: 1919: 1915: 1912: 1910: 1906: 1900: 1897: 1895: 1892: 1890: 1887: 1886: 1884: 1880: 1874: 1873: 1868: 1867: 1865: 1861: 1857: 1850: 1845: 1843: 1838: 1836: 1831: 1830: 1827: 1817: 1813: 1809: 1805: 1800: 1795: 1792:(6): 339–51. 1791: 1787: 1783: 1776: 1773: 1768: 1764: 1759: 1754: 1750: 1746: 1745:J. Biol. Chem 1742: 1735: 1732: 1727: 1723: 1718: 1713: 1709: 1705: 1701: 1697: 1693: 1686: 1683: 1678: 1674: 1669: 1664: 1660: 1656: 1655:J. Biol. Chem 1652: 1645: 1642: 1637: 1633: 1628: 1623: 1619: 1615: 1611: 1607: 1603: 1596: 1593: 1588: 1584: 1579: 1574: 1570: 1566: 1562: 1558: 1554: 1547: 1544: 1539: 1535: 1530: 1525: 1521: 1517: 1516:J. Biol. Chem 1513: 1506: 1503: 1498: 1494: 1490: 1486: 1478: 1475: 1470: 1466: 1461: 1456: 1452: 1448: 1444: 1440: 1436: 1429: 1426: 1421: 1417: 1412: 1407: 1403: 1399: 1396:(5): 963–75. 1395: 1391: 1387: 1380: 1377: 1372: 1368: 1364: 1360: 1356: 1352: 1348: 1344: 1337: 1335: 1331: 1326: 1322: 1318: 1314: 1310: 1306: 1302: 1298: 1291: 1288: 1283: 1279: 1275: 1271: 1267: 1263: 1259: 1255: 1251: 1247: 1240: 1237: 1232: 1228: 1224: 1220: 1215: 1210: 1206: 1202: 1198: 1191: 1188: 1183: 1179: 1174: 1169: 1165: 1161: 1157: 1153: 1149: 1142: 1139: 1134: 1130: 1126: 1122: 1118: 1114: 1107: 1104: 1099: 1095: 1091: 1087: 1083: 1079: 1075: 1071: 1067: 1063: 1055: 1052: 1047: 1043: 1039: 1035: 1031: 1027: 1024:(2): 147–69. 1023: 1019: 1012: 1009: 1004: 1000: 996: 992: 988: 984: 981:(2): 279–90. 980: 976: 968: 965: 960: 956: 951: 946: 941: 936: 932: 928: 924: 920: 916: 909: 906: 901: 897: 893: 889: 885: 881: 878:(2): 263–74. 877: 873: 866: 863: 857: 850: 847: 845: 842: 840: 837: 835: 832: 830: 827: 826: 824: 821: 817: 814: 812: 809: 808: 806: 803: 799: 796: 794: 791: 789: 786: 784: 781: 779: 776: 774: 771: 769: 766: 764: 761: 760: 758: 755: 751: 748: 746: 743: 741: 738: 736: 733: 732: 730: 727: 723: 720: 718: 715: 713: 710: 709: 707: 704: 700: 697: 695: 692: 691: 689: 686: 682: 679: 677: 674: 673: 671: 668: 664: 661: 659: 656: 655: 653: 650: 646: 643: 641: 638: 637: 635: 632: 631: 625: 622: 620: 617: 616: 614: 611: 610: 609: 603: 601: 599: 594: 590: 586: 582: 573: 571: 569: 564: 562: 558: 553: 549: 546: 542: 534: 532: 529: 523: 520: 516: 512: 508: 507:myristoylated 504: 496: 494: 491: 487: 479: 477: 474: 470: 466: 462: 458: 454: 450: 446: 442: 438: 434: 429: 425: 421: 420:transmembrane 417: 409: 407: 405: 401: 397: 393: 389: 385: 381: 377: 373: 369: 368:T lymphocytes 366:receptors on 365: 361: 357: 353: 349: 345: 341: 337: 333: 330:in activated 329: 321: 319: 317: 316:immune system 313: 309: 306: 302: 297: 295: 291: 287: 283: 280:group from a 279: 275: 272: 268: 264: 251: 248: 246: 242: 239: 236: 234: 230: 227: 224: 222: 218: 213: 209: 206: 202: 199: 197: 196:Gene Ontology 193: 190: 187: 184: 181: 178: 174: 171: 168: 166: 162: 159: 156: 154: 150: 147: 144: 142: 138: 135: 134:NiceZyme view 132: 130: 126: 123: 120: 118: 114: 111: 108: 106: 102: 97: 94: 91: 89: 85: 80: 75: 66: 63: 55: 45: 41: 35: 32:This article 30: 21: 20: 4147:Translocases 4144: 4131: 4118: 4105: 4092: 4082:Transferases 4079: 4066: 3923:Binding site 3769:SRC-B family 3738:SRC-A family 3542: 3495:RET receptor 3466:AXL receptor 3388:RYK receptor 3345:DDR receptor 3321:ROR receptor 3297:TIE receptor 3273:LTK receptor 3184:EPH receptor 3151:Trk receptor 3127:HGF receptor 3064:FGF receptor 2871: 2806: 2785: 2591: 2421:eIF-2 kinase 1869: 1789: 1785: 1775: 1748: 1744: 1734: 1699: 1695: 1685: 1658: 1654: 1644: 1609: 1605: 1595: 1560: 1556: 1546: 1519: 1515: 1505: 1488: 1484: 1477: 1442: 1438: 1428: 1393: 1389: 1379: 1349:(1): 65–73. 1346: 1342: 1300: 1296: 1290: 1249: 1245: 1239: 1207:(3): 365–8. 1204: 1200: 1190: 1155: 1151: 1141: 1116: 1112: 1106: 1065: 1061: 1054: 1021: 1017: 1011: 978: 974: 967: 922: 918: 908: 875: 871: 865: 607: 577: 565: 550: 538: 524: 500: 483: 413: 325: 298: 266: 262: 260: 122:BRENDA entry 58: 52:October 2018 49: 33: 3918:Active site 2108:GNA15/GNA16 1894:Calcineurin 1786:Genes Cells 1018:Genes Cells 497:Src and Abl 463:contains a 299:Unlike the 110:IntEnz view 82:Identifiers 4190:Categories 4121:Isomerases 4095:Hydrolases 3962:Regulation 2514:Lim kinase 2465:IÎşB kinase 1986:Transducin 1119:: 259–88. 858:References 583:and tumor 581:metastasis 574:Inhibitors 552:Jak family 503:Src family 480:Regulation 449:Jak family 179:structures 146:KEGG entry 4196:EC 2.7.10 4000:EC number 2872:see also 2778:Apoptosis 2259:Monomeric 1991:Gustducin 1909:G protein 439:) and 3 ( 410:Structure 312:apoptosis 278:phosphate 271:cytosolic 99:Databases 4024:Kinetics 3948:Cofactor 3911:Activity 2730:Tyrosine 2675:Arginine 2592:Tyrosine 1816:24871585 1808:10421843 1485:Oncogene 1371:35630246 1046:38301879 1003:32339052 900:13225245 604:Examples 453:integrin 388:cytokine 322:Function 308:2.7.10.2 290:proteins 250:proteins 238:articles 226:articles 183:RCSB PDB 93:2.7.10.2 4180:Biology 4134:Ligases 3904:Enzymes 2925:2.7.10) 2856:EDARADD 2841:Mucin-4 2580:RPS6KA1 2426:EIF2AK3 1882:Calcium 1767:9242667 1726:9111318 1677:7531704 1636:1848670 1587:8756661 1538:7537732 1497:7539119 1469:8164650 1420:7534229 1363:3103925 1325:2420005 1305:Bibcode 1297:Science 1282:4363527 1274:1709258 1254:Bibcode 1231:5591073 1223:8898190 1182:9736615 1173:1170863 1133:9241420 1098:1105841 1090:7845468 1070:Bibcode 1038:9140060 995:8425221 959:7809124 927:Bibcode 892:8293463 825:family 807:family 759:family 731:family 708:family 690:family 672:family 654:family 636:family 615:family 336:B-cells 269:) is a 205:QuickGO 170:profile 153:MetaCyc 38:Please 4166:Portal 4108:Lyases 3842:family 3803:family 3707:family 3678:family 3654:family 3630:family 3606:family 3582:family 3558:family 3497:family 3468:family 3456:AATYK2 3444:family 3409:family 3390:family 3371:family 3347:family 3323:family 3299:family 3275:family 3186:family 3153:family 3129:family 3117:VEGFR3 3112:VEGFR2 3107:VEGFR1 3100:family 3066:family 3053:PDGFRB 3048:PDGFRA 2994:family 2861:PRKCSH 2700:Other 2649:DYRK1B 2644:DYRK1A 2384:Other 2354:Cyclin 2337:Cyclin 1814:  1806:  1765:  1724:  1717:232098 1714:  1675:  1634:  1627:359893 1624:  1585:  1578:231504 1575:  1536:  1495:  1467:  1460:358656 1457:  1418:  1411:398168 1408:  1390:EMBO J 1369:  1361:  1323:  1280:  1272:  1246:Nature 1229:  1221:  1180:  1170:  1152:EMBO J 1131:  1096:  1088:  1062:Nature 1044:  1036:  1001:  993:  957:  947:  898:  890:  416:ligand 354:) and 274:enzyme 233:PubMed 215:Search 201:AmiGO 189:PDBsum 129:ExPASy 117:BRENDA 105:IntEnz 88:EC no. 4060:Types 3854:ZAP70 3520:STYK1 3485:TYRO3 3451:AATYK 3258:EPHB6 3253:EPHB5 3248:EPHB4 3243:EPHB3 3238:EPHB2 3233:EPHB1 3228:EPHA8 3223:EPHA7 3218:EPHA6 3213:EPHA5 3208:EPHA4 3203:EPHA3 3198:EPHA2 3193:EPHA1 3170:NTRK3 3165:NTRK2 3160:NTRK1 3088:FGFR4 3083:FGFR3 3078:FGFR2 3073:FGFR1 3044:PDGFR 3029:CSF1R 3011:INSRR 3001:IGF1R 2982:ERBB4 2977:ERBB3 2972:ERBB2 2819:Other 2757:both: 2664:DYRK4 2659:DYRK3 2654:DYRK2 2616:PTK2B 2601:ZAP70 2568:ROCK2 2563:ROCK1 2524:LIMK2 2519:LIMK1 2507:IRAK4 2502:IRAK3 2497:IRAK2 2492:IRAK1 2480:IKBKG 2458:GSK3B 2453:GSK3A 2448:GSK-3 2363:Lipid 2314:Rhebs 2225:BSCL2 2220:GNG13 2215:GNG12 2210:GNG11 2205:GNG10 2170:GNGT2 2165:GNGT1 2103:GNA14 2098:GNA13 2093:GNA12 2088:GNA11 2063:GNAT3 2058:GNAT2 2053:GNAT1 2048:GNAI3 2043:GNAI2 2038:GNAI1 2033:GNAO1 1812:S2CID 1367:S2CID 1278:S2CID 1227:S2CID 1094:S2CID 1042:S2CID 999:S2CID 950:45528 896:S2CID 816:ZAP70 545:Zap70 384:Zap70 348:IL-2R 165:PRIAM 4152:list 4145:EC7 4139:list 4132:EC6 4126:list 4119:EC5 4113:list 4106:EC4 4100:list 4093:EC3 4087:list 4080:EC2 4074:list 4067:EC1 3760:YES1 3729:TYK2 3724:JAK3 3719:JAK2 3714:JAK1 3695:SRMS 3642:PYK2 3618:MATK 3594:TNK1 3589:ACK1 3565:ABL1 3432:ROS1 3416:MUSK 3378:PTK7 3359:DDR2 3354:DDR1 3335:ROR2 3330:ROR1 3263:EPHX 3034:FLT3 3006:INSR 2967:EGFR 2807:see 2786:see 2687:McsB 2611:PTK2 2551:PAK4 2546:PAK3 2541:PAK2 2536:PAK1 2475:IKK2 2470:CHUK 2443:GSK2 2438:GSK1 2324:RGKs 2319:Raps 2304:Arfs 2299:Rhos 2292:NRAS 2287:KRAS 2282:HRAS 2272:Rabs 2267:ARFs 2200:GNG8 2195:GNG7 2190:GNG5 2185:GNG4 2180:GNG3 2175:GNG2 2152:GNB5 2147:GNB4 2142:GNB3 2137:GNB2 2132:GNB1 2083:GNAQ 2078:GNAL 2073:GNAS 2068:GNAZ 2001:cGMP 1977:cGMP 1957:cAMP 1927:cAMP 1870:see 1804:PMID 1763:PMID 1722:PMID 1673:PMID 1632:PMID 1583:PMID 1534:PMID 1493:PMID 1465:PMID 1416:PMID 1359:PMID 1343:Cell 1321:PMID 1270:PMID 1219:PMID 1201:Cell 1178:PMID 1129:PMID 1086:PMID 1034:PMID 991:PMID 975:Cell 955:PMID 888:PMID 872:Cell 778:YES1 750:TYK2 745:JAK3 740:JAK2 735:JAK1 722:SRMS 681:PYK2 663:MATK 645:TNK1 640:ACK1 619:ABL1 568:SOCS 561:Jak2 557:Tyk2 541:ITAM 362:and 352:EpoR 334:and 267:nRTK 245:NCBI 186:PDBe 141:KEGG 3849:SYK 3840:SYK 3830:TXK 3825:ITK 3820:BTK 3815:BMX 3810:TEC 3801:TEC 3791:LYN 3786:LCK 3781:HCK 3776:BLK 3755:FYN 3750:FGR 3745:SRC 3705:JAK 3690:BRK 3685:FRK 3676:FRK 3666:FER 3661:FES 3652:FES 3637:FAK 3628:FAK 3613:CSK 3604:CSK 3580:ACK 3570:ARG 3556:ABL 3504:RET 3480:MER 3475:AXL 3397:RYK 3311:TEK 3306:TIE 3287:ALK 3282:LTK 3141:RON 3136:MET 3039:KIT 2623:BTK 2309:Ran 2277:Ras 1863:MAP 1794:doi 1753:doi 1749:272 1712:PMC 1704:doi 1663:doi 1659:270 1622:PMC 1614:doi 1573:PMC 1565:doi 1524:doi 1520:270 1455:PMC 1447:doi 1406:PMC 1398:doi 1351:doi 1313:doi 1301:231 1262:doi 1250:351 1209:doi 1168:PMC 1160:doi 1121:doi 1078:doi 1066:373 1026:doi 983:doi 945:PMC 935:doi 880:doi 849:TXK 844:ITK 839:BTK 834:BMX 829:TEC 823:TEC 811:SYK 805:SYK 798:LYN 793:LCK 788:HCK 783:BLK 773:FYN 768:FGR 763:SRC 757:SRC 729:JAK 717:BRK 712:FRK 706:FRK 699:FER 694:FES 688:FES 676:FAK 670:FAK 658:CSK 652:CSK 634:ACK 624:ARG 613:ABL 528:Abl 515:Csk 441:SH3 437:SH2 433:DNA 400:Btk 396:Syk 392:Lyn 376:Lck 372:Src 364:CD8 360:CD4 344:BCR 340:TCR 286:ATP 221:PMC 177:PDB 42:to 4192:: 2923:EC 2917:: 2741:: 1945:Gi 1941:Gs 1810:. 1802:. 1788:. 1784:. 1761:. 1747:. 1743:. 1720:. 1710:. 1700:17 1698:. 1694:. 1671:. 1657:. 1653:. 1630:. 1620:. 1610:11 1608:. 1604:. 1581:. 1571:. 1561:16 1559:. 1555:. 1532:. 1518:. 1514:. 1489:10 1487:. 1463:. 1453:. 1443:14 1441:. 1437:. 1414:. 1404:. 1394:14 1392:. 1388:. 1365:. 1357:. 1347:49 1345:. 1333:^ 1319:. 1311:. 1299:. 1276:. 1268:. 1260:. 1248:. 1225:. 1217:. 1205:87 1203:. 1199:. 1176:. 1166:. 1156:17 1154:. 1150:. 1127:. 1117:26 1115:. 1092:. 1084:. 1076:. 1064:. 1040:. 1032:. 1020:. 997:. 989:. 979:72 977:. 953:. 943:. 933:. 923:91 921:. 917:. 894:. 886:. 876:76 874:. 358:. 332:T- 318:. 305:EC 261:A 203:/ 4168:: 4154:) 4150:( 4141:) 4137:( 4128:) 4124:( 4115:) 4111:( 4102:) 4098:( 4089:) 4085:( 4076:) 4072:( 3896:e 3889:t 3882:v 3055:) 3046:( 2921:( 2907:e 2900:t 2893:v 2732:: 2713:: 2594:: 2414:2 2409:1 2397:: 2160:Îł 2158:G 2127:β 2125:G 2028:α 2026:G 1979:: 1943:/ 1929:: 1848:e 1841:t 1834:v 1818:. 1796:: 1790:4 1769:. 1755:: 1728:. 1706:: 1679:. 1665:: 1638:. 1616:: 1589:. 1567:: 1540:. 1526:: 1499:. 1471:. 1449:: 1422:. 1400:: 1373:. 1353:: 1327:. 1315:: 1307:: 1284:. 1264:: 1256:: 1233:. 1211:: 1184:. 1162:: 1135:. 1123:: 1100:. 1080:: 1072:: 1048:. 1028:: 1022:1 1005:. 985:: 961:. 937:: 929:: 902:. 882:: 265:( 65:) 59:( 54:) 50:( 36:.

Index

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EC no.
2.7.10.2
IntEnz
IntEnz view
BRENDA
BRENDA entry
ExPASy
NiceZyme view
KEGG
KEGG entry
MetaCyc
metabolic pathway
PRIAM
profile
PDB
RCSB PDB
PDBe
PDBsum
Gene Ontology
AmiGO
QuickGO
PMC
articles
PubMed
articles
NCBI
proteins

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