БИОХИМИЯ, 2020, том 85, вып. 4, с. 476–493
УДК 577.151.36
Каталитическая субъединица PKA как прототип семейства эукариотических протеинкиназ
Обзор
Институт экспериментальной медицины, 197376 Санкт-Петербург, Россия; электронная почта: reichardt@mail.ru
Поступила в редакцию 21.10.2019
После доработки 25.02.2020
Принята к публикации 26.02.2020
DOI: 10.31857/S0320972520040028
КЛЮЧЕВЫЕ СЛОВА: каталитическая субъединица PKA, АТР-связывающий сайт PKА, пептид-связывающий сайт PKА, Thr197 PKA, гидрофобные спины.
Аннотация
Каталитическая субъединица PKА (PKAc) представляет собой практически изолированный киназный домен, консервативный у всех эукариотических протеинкиназ. PKAc состоит из двух долей, образующих каталитическую щель, в которой располагаются: ATP-связывающий участок, пептид-связывающий участок и каталитический сайт. В процессе фолдинга вторичные структуры РКАс укладываются так, что неполярные участки собираются в глобулярное ядро, а подвижные петли и хвосты экспонируются наружу, образуя регуляторные элементы. Синтезированная de novo PKАс подвергается процессингу путем фосфорилирования T-петли. При этом формируется полноценный активный центр, способный высокоаффинно связывать косубстраты. Молекула АТР «склеивает» две доли вместе, а связывание пептидного субстрата завершает сборку активного центра. В результате «каталитическая триада» (γ-фосфат ATP, гидроксил Ser/Thr белка-субстрата и карбоксил Asp166) занимает положение, оптимальное для эффективного катализа. Динамическая реорганизация полярных и гидрофобных взаимодействий в ходе каталитического цикла обеспечивает переход PKАс из открытой конформации в закрытую и обратно. Изучение структурных основ работы ePK необходимо для успешного создания модуляторов ePK.
Текст статьи
Сноски
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Конфликт интересов
Авторы заявляют об отсутствии конфликта интересов.
Соблюдение этических норм
Настоящая работа не содержит каких-либо исследований, в которых были использованы в качестве объектов люди или животные.
Список литературы
1. Walsh, D. A., Perkins, J. P., and Krebs, E. G. (1968) An adenosine 3′,5′-monophosphate-dependent protein kinase from rabbit skeletal muscle, J. Biol. Chem., 243, 3763-3765.
2. Knighton, D. R., Zheng, J. H., Ten Eyck, L. F., Xuong, N. H., Taylor, S. S., and Sowadski, J. M. (1991) Crystal structure of the catalytic subunit of cyclic adenosine monophosphate-dependent protein kinase, Science, 253, 407-414, doi: 10.1126/science.1862342.
3. Zheng, J., Trafny, E. A., Knighton, D. R., Xuong, N. H., Taylor, S. S., Ten Eyck, L. F., and Sowadski, J. M. (1993) 2.2 A refined crystal structure of the catalytic subunit of cAMP-dependent protein kinase complexed with MnATP and a peptide inhibitor, Acta Crystallogr. D Biol. Crystallogr., 49, 362-365, doi: 10.1107/S0907444993000423.
4. Hanks, S. K., and Hunter, T. (1995) Protein kinases 6. The eukaryotic protein kinase superfamily: kinase (catalytic) domain structure and classification, FASEB J., 9, 576-596.
5. Taylor, S. S., Knighton, D. R., Zheng, J., Ten Eyck, L. F., and Sowadski, J. M. (1992) cAMP-dependent protein kinase and the protein kinase family, Faraday Discuss., 93, 143-152, doi: 10.1039/fd9929300143.
6. Taylor, S. S., Radzio-Andzelm, E., Knighton, D. R., Ten Eyck, L. F., Sowadski, J. M., Herberg, F. W., Yonemoto, W., and Zheng, J. (1993) Crystal structures of the catalytic subunit of cAMP-dependent protein kinase reveal general features of the protein kinase family, Receptor., 3, 165-172.
7. Taylor, S. S., Zheng, J., Radzio-Andzelm, E., Knighton, D. R., Ten Eyck, L. F., Sowadski, J. M., Herberg, F. W., and Yonemoto, W. M. (1993) cAMP-dependent protein kinase defines a family of enzymes, Philos. Trans. R. Soc. Lond. B Biol. Sci., 340, 315-324, doi: 10.1098/rstb.1993.0073.
8. Taylor, S. S., Knighton, D. R., Zheng, J., Sowadski, J. M., Gibbs, C. S., and Zoller, M. J. (1993) A template for the protein kinase family, Trends Biochem. Sci., 18, 84-89, doi: 10.1016/0968-0004(93)80001-r.
9. Taylor, S. S., and Kornev, A. P. (2012) in: Quantitative Biology: From Molecular to Cellular Systems (Wall, M. E., ed.), CRC Press, pp. 267-298.
10. Taylor, S. S., Zhang, P., Steichen, J. M., Keshwani, M. M., and Kornev, A. P. (2013) PKA: lessons learned after twenty years, Biochim. Biophys. Acta, 1834, 1271-1278, doi: 10.1016/j.bbapap.2013.03.007.
11. Taylor, S. S., Meharena, H. S., and Kornev, A. P. (2019) Evolution of a dynamic molecular switch, IUBMB Life, 71, 672-684, doi: 10.1002/iub.2059.
12. Fischer, E. H., and Krebs, E. G. (1955) Conversion of phosphorylase b to phosphorylase a in muscle extracts, J. Biol. Chem., 216, 121-132.
13. Северин Е. С., Кочеткова М. Н. (1985) Роль фосфорилирования в регуляции клеточной активности, Наука, Москва.
14. Graves, J. D., and Krebs, E. G. (1999) Protein phosphorylation and signal transduction, Pharmacol. Ther., 82, 111-121, doi: 10.1016/s0163-7258(98)00056-4.
15. Cohen, P. (2000) The regulation of protein function by multisite phosphorylation – a 25 year update, Trends Biochem. Sci., 25, 596-601, doi: 10.1016/s0968-0004(00)01712-6.
16. Hunter, T. (2000) Signaling-2000 and beyond, Cell, 100, 113-127, doi: 10.1016/s0092-8674(00)81688-8.
17. Jeske, L., Placzek, S., Schomburg, I., Chang, A., and Schomburg, D. (2019) BRENDA in 2019: a european ELIXIR core data resource, Nucleic Acids Res., 47, 542-549, doi: 10.1093/nar/gky1048.
18. Гусев Н. Б. (2000) Протеинкиназы: строение, классификация, свойства и биологическая роль, СОЖ, 6, 4-12.
19. Manning, G., Whyte, D. B., Martinez, R., Hunter, T., and Sudarsanam, S. (2002) The protein kinase complement of the human genome, Science, 298, 1912-1934, doi: 10.1126/science.1075762.
20. Olsen, J. V., Blagoev, B., Gnad, F., Macek, B., Kumar, C., Mortensen, P., and Mann, M. (2006) Global, in vivo, and site-specific phosphorylation dynamics in signaling networks, Cell, 127, 635-648, doi: 10.1016/j.cell.2006.09.026.
21. Gschwind, A., Fischer, O. M., and Ullrich, A. (2004) The discovery of receptor tyrosine kinases: targets for cancer therapy, Nat. Rev. Cancer, 4, 361-370, doi: 10.1038/nrc1360.
22. Bradshaw, J. M. (2010) The Src, Syk, and Tec family kinases: distinct types of molecular switches, Cell Signal., 22, 1175-1184, doi: 10.1016/j.cellsig.2010.03.001.
23. Gaestel, M. (2016) MAPK-activated protein kinases (MKs): novel insights and challenges, Front. Cell Dev. Biol., 3, 88, doi: 10.3389/fcell.2015.00088.
24. Waters, M. J. (2016) The growth hormone receptor, Growth Horm. IGF Res., 28, 6-10, doi: 10.1016/j.ghir.2015.06.001.
25. Kim, J. J., Lorenz, R., Arold, S. T., Reger, A. S., Sankaran, B., Casteel, D. E., Herberg, F. W., and Kim, C. (2016) Crystal structure of PKG I:cGMP complex reveals a cGMP-mediated dimeric Interface that facilitates cGMP-induced activation, Structure, 24, 710-720, doi: 10.1016/j.str.2016.03.009.
26. Isakov, N. (2018) Protein kinase C (PKC) isoforms in cancer, tumor promotion and tumor suppression, Semin. Cancer Biol., 48, 36-52, doi: 10.1016/j.semcancer.2017.04.012.
27. Brzozowski, J. S., and Skelding, K. A. (2019) The multi-functional calcium/calmodulin stimulated protein kinase (CaMK) family: emerging targets for anti-cancer therapeutic intervention, Pharmaceuticals (Basel), 12, pii: E8, doi: 10.3390/ph12010008.
28. Pawson, T., and Nash, P. (2003) Assembly of cell regulatory systems through protein interaction domains, Science, 300, 445-452, doi: 10.1126/science.1083653.
29. Brown, N. R., Korolchuk, S., Martin, M. P., Stanley, W. A., Moukhametzianov, R., Noble, M. E. M., and Endicott, J. A. (2015) CDK1 structures reveal conserved and unique features of the essential cell cycle CDK, Nat. Commun., 6, 6769, doi: 10.1038/ncomms7769.
30. Bibby, A. C., and Litchfield, D. W. (2005) The multiple personalities of the regulatory subunit of protein kinase CK2: CK2 dependent and CK2 independent roles reveal a secret identity for CK2 beta, Int. J. Biol. Sci., 1, 67-79, doi: 10.7150/ijbs.1.67.
31. Taylor, S. S., Ilouz, R., Zhang, P., and Kornev, A. P. (2012) Assembly of allosteric macromolecular switches: lessons from PKA, Nat. Rev. Mol. Cell Biol., 13, 646-658, doi: 10.1038/nrm3432.
32. Shabb, J. B. (2001) Physiological substrates of cAMP-dependent protein kinase, Chem. Rev., 101, 2381-2411.
33. Bossemeyer, D., Engh, R. A., Kinzel, V., Ponstingl, H., and Huber, R. (1993) Phosphotransferase and substrate binding mechanism of the cAMP-dependent protein kinase catalytic subunit from porcine heart as deduced from the 2.0 A structure of the complex with Mn2+ adenylyl imidodiphosphate and inhibitor peptide PKI(5-24), EMBO J., 12, 849-859.
34. Taylor, S. S., Yang, J., Wu, J., Haste, N. M., Radzio-Andzelm, E., and Anand, G. (2004) PKA: a portrait of protein kinase dynamics, Biochim. Biophys. Acta, 1697, 259-269, doi: 10.1016/j.bbapap.2003.11.029.
35. Johnson, L. N., Noble, M. E., and Owen, D. J. (1996) Active and inactive protein kinases: structural basis for regulation, Cell, 85, 149-158, doi: 10.1016/s0092-8674(00)81092-2.
36. Johnson, L. N., Lowe, E. D., Noble, M. E., and Owen, D. J. (1998) The eleventh datta lecture. The structural basis for substrate recognition and control by protein kinases, FEBS. Lett., 430, 1-11, doi: 10.1016/s0014-5793(98)00606-1.
37. Johnson, D. A., Akamine, P., Radzio-Andzelm, E., Madhusudan, M., and Taylor, S. S. (2001) Dynamics of cAMP-dependent protein kinase, Chem. Rev., 101, 2243-2270.
38. Kornev, A. P., Haste, N. M., Taylor, S. S., and Eyck, L. F. (2006) Surface comparison of active and inactive protein kinases identifies a conserved activation mechanism, Proc. Natl. Acad. Sci. USA, 103, 17783-17788, doi: 10.1073/pnas.0607656103.
39. Kornev, A. P., and Taylor, S. S. (2015) Dynamics-driven allostery in protein kinases, Trends Biochem. Sci., 40, 628-647, doi: 10.1016/j.tibs.2015.09.002.
40. McClendon, C. L., Kornev, A. P., Gilson, M. K., and Taylor, S. S. (2014) Dynamic architecture of a protein kinase, Proc. Natl. Acad. Sci. USA, 111, E4623-E4631, doi: 10.1073/pnas.1418402111.
41. Gangal, M., Clifford, T., Deich, J., Cheng, X., Taylor, S. S., and Johnson, D. A. (1999) Mobilization of the A-kinase N-myristate through an isoform-specific intermolecular switch, Proc. Natl. Acad. Sci. USA, 96, 12394-12399, doi: 10.1073/pnas.96.22.12394.
42. Herberg, F. W., Zimmermann, B., McGlone, M., and Taylor, S. S. (1997) Importance of the A-helix of the catalytic subunit of cAMP-dependent protein kinase for stability and for orienting subdomains at the cleft interface, Protein Sci., 6, 569-579, doi: 10.1002/pro.5560060306.
43. Bossemeyer, D. (1994) The glycine-rich sequence of protein kinases: a multifunctional element, Trends Biochem. Sci., 19, 201-205, doi: 10.1016/0968-0004(94)90022-1.
44. Grant, B. D., Hemmer, W., Tsigelny, I., Adams, J. A., and Taylor, S. S. (1998) Kinetic analyses of mutations in the glycine-rich loop of cAMP-dependent protein kinase, Biochemistry, 37, 7708-7715, doi: 10.1021/bi972987w.
45. Aimes, R. T., Hemmer, W., and Taylor, S. S. (2000) Serine-53 at the tip of the glycine-rich loop of cAMP-dependent protein kinase: role in catalysis, P-site specificity, and interaction with inhibitors, Biochemistry, 39, 8325-8332, doi: 10.1021/bi992800w.
46. Taylor, S. S., and Kornev, A. P. (2011) Protein kinases: evolution of dynamic regulatory proteins, Trends Biochem. Sci., 36, 65-77, doi: 10.1016/j.tibs.2010.09.006.
47. Kornev, A. P., and Taylor, S. S. (2010) Defining the conserved internal architecture of a protein kinase, Biochim. Biophys. Acta, 1804, 440-444, doi: 10.1016/j.bbapap.2009.10.017.
48. Steichen, J. M., Kuchinskas, M., Keshwani, M. M., Yang, J., Adams, J. A., and Taylor, S. S. (2012) Structural basis for the regulation of protein kinase A by activation loop phosphorylation, J. Biol. Chem., 287, 14672-14680, doi: 10.1074/jbc.M111.335091.
49. Kim, J., Ahuja, L. G., Chao, F. A., Xia, Y., McClendon, C. L., Kornev, A. P., Taylor, S. S., and Veglia, G. (2017) A dynamic hydrophobic core orchestrates allostery in protein kinases, Sci. Adv., 3, e1600663, doi: 10.1126/sciadv.1600663.
50. Taylor, S. S., Shaw, A. S., Kannan, N., and Kornev, A. P. (2015) Integration of signaling in the kinome: architecture and regulation of the αC Helix, Biochim. Biophy. Acta, 1854, 1567-1574, doi: 10.1016/j.bbapap.2015.04.007.
51. Madhusudan, Trafny, E. A., Xuong, N. H., Adams, J. A., Ten Eyck, L. F., Taylor, S. S., and Sowadski, J. M. (1994) cAMP-dependent protein kinase: crystallographic insights into substrate recognition and phosphotransfer, Protein Sci., 3, 176-187, doi: 10.1002/pro.5560030203.
52. Zhou, J., and Adams, J. A. (1997) Is there a catalytic base in the active site of cAMP-dependent protein kinase? Biochemistry, 36, 2977-2984, doi: 10.1021/bi9619132.
53. Valiev, M., Kawai, R., Adams, J. A., Weare, J. H. (2003) The role of the putative catalytic base in the phosphoryl transfer reaction in a protein kinase: first-principles calculations, J. Am. Chem. Soc., 125, 9926-9927, doi: 10.1021/ja029618u.
54. Endicott, J. A., Noble, M. E., and Johnson, L. N. (2012) The structural basis for control of eukaryotic protein kinases, Annu. Rev. Biochem., 81, 587-613, doi: 10.1146/annurev-biochem-052410-090317.
55. Nolen, B., Taylor, S., and Ghosh, G. (2004) Regulation of protein kinases; controlling activity through activation segment conformation, Mol. Cell, 15, 661-675, doi: 10.1016/j.molcel.2004.08.024.
56. Hubbard, S. R. (1997) Crystal structure of the activated insulin receptor tyrosine kinase in complex with peptide substrate and ATP analog, EMBO J., 16, 5572-5581, doi: 10.1093/emboj/16.18.5572.
57. Wood, D. J., and Endicott, J. A. (2018) Structural insights into the functional diversity of the CDK-cyclin family, Open Biol., 8, pii: 180112, doi: 10.1098/rsob.180112.
58. Gógl, G., Kornev, A. P., Reményi, A., and Taylor, S. S. (2019) Disordered protein kinase regions in regulation of kinase domain cores, Trends Biochem. Sci., 44, 300-311, doi: 10.1016/j.tibs.2018.12.002.
59. Kornev, A. P., Taylor, S. S., and Ten Eyck, L. F. (2008) A helix scaffold for the assembly of active protein kinases, Proc. Natl. Acad. Sci. USA, 105, 14377-14382, doi: 10.1073/pnas.0807988105.
60. Niefind, K., Putter, M., Guerra, B., Issinger, O. G., and Schomburg, D. (1999) GTP plus water mimic ATP in the active site of protein kinase CK2, Nat. Struct. Biol., 6, 1100-1103, doi: 10.1038/70033.
61. Niefind, K., and Issinger, O. G. (2010) Conformational plasticity of the catalytic subunit of protein kinase CK2 and its consequences for regulation and drug design, Biochim. Biophys. Acta, 804, 484-492, doi: 10.1016/j.bbapap.2009.09.022.
62. Akamine, P., Madhusudan, Wu, J., Xuong, N.-H., Ten Eyck, L. F., and Taylor, S. S. (2003) Dynamic features of cAMP-dependent protein kinase revealed by apoenzyme crystal structure, J. Mol. Biol. 327, 159-171, doi: 10.1016/s0022-2836(02)01446-8.
63. Bastidas, A. C., Wu, J., and Taylor, S. S. (2015) Molecular features of product release for the PKA catalytic cycle, Biochemistry, 54, 2-10, doi: 10.1021/bi500684c.
64. Moore, M. J., Adams, J. A., and Taylor, S. S. (2003) Structural basis for peptide binding in protein kinase A. Role of glutamic acid 203 and tyrosine 204 in the peptide-positioning loop, J. Biol. Chem., 278, 10613-10618, doi: 10.1074/jbc.M210807200.
65. Shaltiel, S., Cox, S., and Taylor, S. S. (1998) Conserved water molecules contribute to the extensive network of interactions at the active site of protein kinase A, Proc. Natl. Acad. Sci. USA, 95, 484-491, doi: 10.1073/pnas.95.2.484.
66. Gerlits, O., Weiss, K. L., Blakeley, M. P., Veglia, G., Taylor, S. S., and Kovalevsky, A. (2019) Zooming in on protons: neutron structure of protein kinase A trapped in a product complex, Sci. Adv., 5, eaav0482, doi: 10.1126/sciadv.aav0482.
67. Rubenstein, E. M., and Schmidt, M. C. (2007) Mechanisms regulating the protein kinases of Saccharomyces cerevisiae, Eukaryot. Cell, 6, 571-583, doi: 10.1128/EC.00026-07.
68. Kyriakis, J. M., and Avruch, J. (2012) Mammalian MAPK signal transduction pathways activated by stress and inflammation: a 10-year update, Physiol. Rev., 92, 689-737, doi: 10.1152/physrev.00028.2011.
69. Cheng, X., Ma, Y., Moore, M., Hemmings, B. A., and Taylor, S. S. (1998) Phosphorylation and activation of cAMP-dependent protein kinase by phosphoinositide-dependent protein kinase, Proc. Natl. Acad. Sci. USA, 95, 9849-9854, doi: 10.1073/pnas.95.17.9849.
70. Moore, M. J., Kanter, J. R., Jones, K. C., and Taylor, S. S. (2002) Phosphorylation of the catalytic subunit of protein kinase A. Autophosphorylation versus phosphorylation by phosphoinositide-dependent kinase-1, J. Biol. Chem., 277, 47878-47884, doi: 10.1074/jbc.M204970200.
71. Di Blasio, L., Gagliardi, P. A., Puliafito, A., and Primo, L. (2017) Serine/threonine kinase 3-phosphoinositide-dependent protein kinase-1 (PDK1) as a key regulator of cell migration and cancer dissemination, Cancers (Basel), 9, 25, doi: 10.3390/cancers9030025.
72. Yonemoto, W., McGlone, M. L., Grant, B., and Taylor, S. S. (1997) Autophosphorylation of the catalytic subunit of cAMP-dependent protein kinase in Escherichia coli, Protein Eng., 10, 915-925, doi: 10.1093/protein/10.8.915.
73. Millward, T. A., Zolnierowicz, S., and Hemmings, B. A. (1999) Regulation of protein kinase cascades by protein phosphatase 2A, Trends Biochem. Sci., 24, 186-191, doi: 10.1016/s0968-0004(99)01375-4.
74. Xu, X., Chen, Y., Fu, Q., Ni, D., Zhang, J., Li, X., and Lu, S. (2019) The chemical diversity and structure-based discovery of allosteric modulators for the PIF-pocket of protein kinase PDK1, J. Enzyme Inhib. Med. Chem., 34, 361-374, doi: 10.1080/14756366.2018.1553167.
75. Newton, A. C. (2003) Regulation of the ABC kinases by phosphorylation: protein kinase C as a paradigm, Biochem. J., 370, 361-371, doi: 10.1042/BJ20021626.
76. Stempka, L., Schnolzer, M., Radke, S., Rincke, G., Marks, F., and Gschwendt, M. (1999) Requirements of protein kinase cdelta for catalytic function. Role of glutamic acid 500 and autophosphorylation on serine 643, J. Biol. Chem., 274, 8886-8892, doi: 10.1074/jbc.274.13.8886.
77. Yang, J., Ten Eyck, L. F., Xuong, N. H., and Taylor, S. S. (2004) Crystal structure of a cAMP-dependent protein kinase mutant at 1.26A: new insights into the catalytic mechanism, J. Mol. Biol., 336, 473-487, doi: 10.1016/j.jmb.2003.11.044.
78. Adams, J. A. (2001) Kinetic and catalytic mechanisms of protein kinases, Chem. Rev., 101, 2271-2290, doi: 10.1021/cr000230w.
79. Lassila, J. K., Zalatan, J. G., and Herschlag, D. (2011) Biological phosphoryl-transfer reactions: understanding mechanism and catalysis, Annu. Rev. Biochem., 80, 669-702, doi: 10.1146/annurev-biochem-060409-092741.
80. Schwartz, P. A., and Murray, B. W. (2011) Protein kinase biochemistry and drug discovery, Bioorg. Chem., 39, 192-210, doi: 10.1016/j.bioorg.2011.07.004.
81. Montenegro, M., Garcia-Viloca, M., Lluch, J. M., and González-Lafont, A. (2011) QM/MM study of the phosphoryl transfer to the Kemptide substrate catalyzed by protein kinase A. The effect of the phosphorylation state of the protein on the mechanism, Phys. Chem. Chem. Phys., 13, 530-539, doi: 10.1039/c0cp01062f.
82. Wang, Z., and Cole, P. A. (2014) Catalytic mechanisms and regulation of protein kinases, Methods Enzymol., 548, 1-21, doi: 10.1016/B978-0-12-397918-6.00001-X.
83. Кочетков С. Н., Габибов А. Г., Северин Е. С. (1984) Механизмы переноса фосфорильной группы в ферментативных реакциях, Биоорг. химия, 10, 1301-1325.
84. Skamnaki, V. T., Owen, D. J., Noble, M. E., Lowe, E. D., Lowe, G., Oikonomakos, N. G., and Johnson, L. N. (1999) Catalytic mechanism of phosphorylase kinase probed by mutational studies, Biochemistry, 38, 14718-14730, doi: 10.1021/bi991454f.
85. Madhusudan, Akamine, P., Xuong, N. H., and Taylor, S. S. (2002) Crystal structure of a transition state mimic of the catalytic subunit of cAMP-dependent protein kinase, Nat. Struct. Biol., 9, 273-277, doi: 10.1038/nsb780.
86. Shan, Y., Seeliger, M. A., Eastwood, M. P., Frank, F., Xu, H., Jensen, M. Ø., Dror, R. O., Kuriyan, J., and Shaw, D. E. (2009) A conserved protonation-dependent switch controls drug binding in the Abl kinase, Proc. Natl. Acad. Sci. USA, 106, 139-144, doi: 10.1073/pnas.0811223106.
87. Xu, W., Doshi, A., Lei, M., Eck, M. J., and Harrison, S. C. (1999) Crystal structures of c-Src reveal features of its autoinhibitory mechanism, Mol. Cell, 3, 629-638, doi: 10.1016/s1097-2765(00)80356-1.
88. Huse, M., and Kuriyan, J. (2002) The conformational plasticity of protein kinases, Cell, 109, 275-282, doi: 10.1016/s0092-8674(02)00741-9.
89. Cohen, P. (2002) Protein kinases – the major drug targets of the twenty-first century? Nat. Rev. Drug Discov., 1, 309-315, doi: 10.1038/nrd773.
90. Рейхардт Б. А., Куликова О. Г., и Сапронов Н. С. (2002) Терапевтический потенциал модуляторов протеинкиназы СК2, Вестник АМН, 12, 20-24.
91. Bhullar, K. S., Lagarón, N. O., McGowan, E. M., Parmar, I., Jha, A., Hubbard, B. P., and Rupasinghe, H. P. V. (2018) Kinase-targeted cancer therapies: progress, challenges and future directions, Mol. Cancer, 17, 48, doi: 10.1186/s12943-018-0804-2.
92. Kannaiyan, R., and Mahadevan, D. (2018) A comprehensive review of protein kinase inhibitors for cancer therapy, Expert. Rev. Anticancer Ther., 18, 1249-1270, doi: 10.1080/14737140.2018.1527688.
93. Patterson, H., Nibbs, R., McInnes, I., and Siebert, S. (2014) Protein kinase inhibitors in the treatment of inflammatory and autoimmune diseases, Clin. Exp. Immunol., 76, 1-10, doi: 10.1111/cei.12248.
94. Castello, J., Ragnauth, A., Friedman, E., and Rebholz, H. (2017) CK2-an emerging target for neurological and psychiatric disorders, Pharmaceuticals (Basel), 10, 7, doi: 10.3390/ph10010007.
95. Saad, N. S., Elnakish, M. T., Ahmed, A. A. E., and Janssen, P. M. L. (2018) Protein kinase A as a promising target for heart failure drug development, Arch. Med. Res., 49, 530-537, doi: 10.1016/j.arcmed.2018.12.008.
96. Yan, Z., Gibson, S. A., Buckley, J. A., Qin, H., and Benveniste, E. N. (2018) Role of the JAK/STAT signaling pathway in regulation of innate immunity in neuroinflammatory diseases, Clin. Immunol., 189, 4-13, doi: 10.1016/j.clim.2016.09.014.
97. DuShane, J. K., and Maginnis, M. S. (2019) Human DNA virus exploitation of the MAPK-ERK cascade, Int. J. Mol. Sci., 20, 3427, doi: 10.3390/ijms20143427.
98. Batool, M., Ahmad, B., and Choi, S. (2019) A structure-based drug discovery paradigm, Int. J. Mol. Sci., 20, pii: E2783, doi: 10.3390/ijms20112783.
99. Roskoski, R. Jr. (2016) Classification of small molecule protein kinase inhibitors based upon the structures of their drug-enzyme complexes, Pharmacol. Res., 103, 26-48, doi: 10.1016/j.phrs.2015.10.021.
100. Eglen, R., and Reisine, T. (2011) Drug discovery and the human kinome: recent trends, Pharmacol. Ther., 130, 144-156, doi: 10.1016/j.pharmthera.2011.01.007.
101. Jenardhanan, P., Panneerselvam, M., and Mathur, P. P. (2019) Targeting kinase interaction networks: a new paradigm in PPI based design of kinase inhibitors, Curr. Top. Med. Chem., 19, 467-485, doi: 10.2174/1568026619666190304155711.
102. Fabbro, D., Cowan-Jacob, S. W., and Moebitz, H. (2015) Ten things you should know about protein kinases: IUPHAR Review 14, Br. J. Pharmacol., 172, 2675-2700, doi: 10.1111/bph.13096.
103. Бородинова А. А., Зюзина А. Б., и Балабан П. М. (2017) Роль атипичных протеинкиназ в поддержании долговременной памяти и синаптической пластичности, Биохимия, 82, 372-388.