Receptor tyrosine kinase signal transduction and the molecular basis of signalling specificity

Receptor Tyrosine Kinases: Structure, Functions and Role in Human Disease

Volumn , Issue , 2015, Pages 51-76

  De Meyts, Pierre ^a  

^a De Meyts R and D Consulting   (Belgium)

Author keywords

[No Author keywords available]

Indexed keywords

EID: 84925180573     PISSN: None     EISSN: None     Source Type: Book    
DOI: 10.1007/978-1-4939-2053-2_4     Document Type: Chapter

References (126)

1. Cohen S, Levi-Montalcini R, Hamburger V. A nerve growth-stimulating factor isolated from Sarcomas 37 and 180. Proc Natl Acad Sci. 1954;40:1014-8.
2. Cohen S. Isolation of a mouse submaxillary gland protein accelerating incisor eruption and eyelid opening in the new-born animal. J Biol Chem. 1962;237:1555-62.
3. Ullrich A, Coussens L, Hayflick JS, Dull TJ, Gray A, Tam AW, Lee Y, Yarden Y, Libermann TA, Schlessinger J, Downward J, Mayes ELV, Whittle N, Waterfield M, Seeburg P. Human epidermal growth factor receptor cDNA sequence and aberrant expression of the amplified gene in A431 epidermoid carcinoma cells. Nature. 1984;309:418-25.
4. Ullrich A, Bell JR, Chen EY, Herrera R, Petruzelli LM, Dull TJ, Grey A, Coussens L, Liao Y-C, Tsubokawa M, Grunfeld C, Rosen OM, Ramachandran J. Human insulin receptor and its relationship to the tyrosine kinase family of oncogenes. Nature. 1985;313:756-61.
5. Ebina Y, Ellis L, Jarnagin K, Edery M, Graf L, Clauser E, Ou J-H, Masiarz F, Kan YW, Goldfine ID, Roth RA, Rutter WJ. The human Insulin receptor cDNA: the structural basis for hormone - activated transmembrane signalling. Cell. 1985;40:747-58.
6. Ullrich A, Gray A, Tam AW, Yang-Feng T, Tsubokawa M, Collins C, Henzel W, Le Bon T, Kathuria S, Chen E, Jacobs S, Francke U, Ramachandran J, Fujita-Yamaguchi Y. Insulin-like growth factor-I receptor primary structure: comparison with insulin receptor suggests structural determinants that define functional specificity. EMBO J. 1986;5:2503-12.
7. Coussens L, Van Beveren C, Smith D, Chen E, Mitchell RL, Isacke CM, Verma IM, Ullrich A. Structural alteration of viral homologue of receptor proto-oncogene fms at carboxyl terminus. Nature. 1986;321:277-81.
8. Yarden Y, Escobedo JA, Kwang W-J, Yang-Feng TL, Daniel TO, Tremble PM, Chen EY, Ando ME, Harkins NR, Francke U, Fried UA, Ullrich A, Williams LT. Structure of the receptor for platelet-derived growth factor helps define a family of closely related growth-factor receptors. Nature. 1986;323:226-32.
9. Yarden Y, Ullrich A. Growth-factor receptor tyrosine kinases. Ann Rev Biochem. 1988;57:443-78.
10. Ullrich A, Schlessinger J. Signal transduction by receptors with tyrosine kinase activity. Cell. 1990;61:203-12.
11. Schlessinger J, Ullrich A. Growth factor signalling by receptor tyrosine kinases. Neuron. 1992;9:383-91.
12. Van der Geer P, Hunter T, Lindberg RA. Receptor protein-tyrosine kinases and their signal transduction pathways. Ann Rev Cell Bio. 1994;10:251-337.
13. Heldin CH. Dimerization of cell surface receptors in signal transduction. Cell. 1995;80:213-23.
14. Schlessinger J. Cell signalling by receptor tyrosine kinases. Cell. 2000;103:211-25.
15. Hunter T. Signaling - 2000 and beyond. Cell. 2000;100:113-27.
16. Blume-Jensen P, Hunter T. Oncogenic kinase signalling. Nature. 2001;411:355-65.
17. Hubbard SR, Miller WT. Receptor tyrosine kinases: mechanisms of activation and signaling. Curr Opin Cell Biol. 2007;19:117-23.
18. De Meyts P. The insulin receptor: a prototype for dimeric, allosteric membrane receptors? Trends Biochem Sci. 2008;33:376-84.
19. De Meyts P, Gauguin L, Svendsen AM, Sarhan M, Knudsen L, Nøhr J, Kiselyov VV. Structural basis of allosteric interactions in the insulin/relaxin peptide family. Implications for other receptor tyrosine kinases and G protein-coupled receptors. Ann NY Acad Sci. 2009;1160:45-53.
20. Lemmon MA, Schlessinger J. Cell signalling by receptor tyrosine kinases. Cell. 2010;141:1117-34.
21. Schlessinger J. Receptor tyrosine kinases: legacy of the first two decades. Cold Spring Harb Perspect Biol 2014;6(3). pii: a008912, doi: 10.1101/cshperspect.a008912.
22. Hunter T. The genesis of tyrosine phosphorylation. Cold Spring Harb Perspect Biol 2014;6(5):a020644, doi: 10.1101/cshperspecta620644.
23. Lemmon MA, Schlessinger J and Ferguson KM. The EGFR family: not so prototypical receptor tyrosine kinases. Cold Spring Harb Perspect Biol 2014;6(4):a020768, doi: 10.1101/cshperspecta020768.
24. Honegger AM, Kris RM, Ullrich A, Schlessinger J. Evidence that autophosphorylation of solubilized receptors for epidermal growth factor is mediated by intermolecular cross-phosphorylation. Proc Natl Acad Sci. 1989;86:925-9.
25. de Vos AM, Ultsch M, Kossiakoff AA. Human growth hormone and extracellular domain of its receptor: crystal structure of the complex. Science. 1992;255:306-12.
26. Wiesmann C, Ultsch MH, Bass CH, de Vos AM. Crystal structure of nerve growth factor in complex with the ligand-binding domain of the TrkA receptor. Nature. 1999;401:184-8.
27. Yuzawa S, Opatowsky Y, Zhang Z, Mandiyan V, Lax I, Schlessinger J. Structural basis for the activation of the receptor tyrosine kinase KIT by stem cell factor. Cell. 2007;130:323-34.
28. Ogiso H, Ishitani R, Nureki O, Fukai S, Yamanaka M, Kim JH, Saito K, Sakamoto A, Inoue M, Shirozou M, Yokoyama S. Crystal structure of the complex of human epidermal growth factor and receptor extracellular domains. Cell. 2002;110:770-87.
29. Cherezov V, Rosenbaum DM, Hanson MA, Rasmussen CG, Thian FS, Kobilka TS, Choi HJ, Kuhn P, Weis WI, Kobilka BK, Stevens RC. High-resolution crystal structure of an engineered human beta(2)-adrenergic G protein-coupled receptor. Science. 2007;318:1258-65.
30. Monod J, Wyman J, Changeux JP. On the structure of allosteric transitions. a plausible model. J Mol Biol. 1965;12:88-118.
31. Koshland DE, Nemethy G, Filmer D. Comparison of experimental binding data and theoretical models in proteins containing subunits. Biochemistry. 1966;5:365-85.
32. Levitzki A, Koshland DE. Negative cooperativity in regulatory enzymes. Proc Natl Acad Sci. 1969;62:1121-8.
33. Schlessinger J, Levitzki A. Molecular basis for negative cooperativity in rabbit muscle glyceraldehyde-3-phosphate dehydrogenase. J Mol Biol. 1974;82:547-61.
34. De Meyts P, Roth J, Neville Jr DM, Gavin 3rd JR, Lesniak MA. Insulin interactions with its receptors: experimental evidence for negative cooperativity. Biochem Biophys Res Commun. 1973;55:154-61.
35. Christoffersen CT, Bornfeldt KE, Rotella CM, Gonzales N, Vissing H, Shymko RM, ten Hoeve J, Groffen J, Heisterkamp N, De Meyts P. Negative cooperativity in the insulin-like growth factor-I (IGF-I) receptor and a chimeric IGF-I/insulin receptor. Endocrinology. 1994;135:472-5.
36. 125 -I nerve growth factor in embryonic heart and brain. J Biol Chem. 1974;249:5918-23.
37. Zampieri N, Chao MV. The p75 NGF receptor exposed. Science. 2004;304:833-4.
38. Cuatrecasas P, Hollenberg MD. Binding of insulin and other hormones to non-receptor materials: saturability, specificity and apparent "negative cooperativity". Biochem Biophys Res Commun. 1975;62:31-41.
39. Rao CV, Carman FR, Chegini N, Schultz GS. Binding sites for epidermal growth factor in human fetal membranes. J Clin Endo Metab. 1984;58:1034-42.
40. Prahl M, Nederman T, Carlsson J, Sjödin L. Binding of epidermal growth factor (EGF) to a cultured human glioma cell line. J Recept Res. 1991;11:791-812.
41. De Meyts P. Cooperative properties of hormone receptors in cell membranes. J Supramol Struct. 1976;4:241-58.
42. Macdonald JL, Pike LJ. Heterogeneity in EGF-binding affinities arise from negative cooperativity in an aggregating system. Proc Natl Acad Sci U S A. 2008;105:112-7.
43. Wofsy C, Goldstein B, Lund K, Wiley HS. Implications of epidermal growth factor (EGF) induced EGF receptor aggregation. Biophys J. 1992;63:98-110.
44. De Meyts P. The structural basis of insulin and insulin-like growth factor-I (IGF-I) receptor binding and negative cooperativity, and its relevance to mitogenic versus metabolic signaling. Diabetologia. 1994;37 suppl 2:S135-48.
45. Alvarado D, Klein DE, Lemmon MA. Structural basis for negative cooperativity in growth factor binding to an EGF receptor. Cell. 2010;142:568-79.
46. Leahy DJ. The ins and outs of EGFR asymmetry. Cell. 2010;142:513-5.
47. Limbird L, De Meyts P, Lefkowitz RJ. Beta-adrenergic receptors: evidence for negative cooperativity. Biochem Biophys Res Commun. 1975;64:1160-8.
48. Urizar E, Montanelli L, Loy T, Bonomi M, Swillens S, Gales C, Bouvier M, Smits G, Vassart G, Costagliola S. Glycoprotein hormone receptors: link between receptor homodimerization and negative cooperativity. EMBO J. 2005;24:1954-64.
49. Christopoulos A, Kenakin T. G protein-coupled receptor allosterism and complexing. Pharmacol Rev. 2002;54:323-74.
50. Springael JY, Urizar E, Costagliola S, Vassart G, Parmentier M. Allosteric properties of G protein-coupled oligomers. Pharmacol Ther. 2007;115:410-8.
51. Svendsen AM, Vrecl M, Knudsen L, Heding A, Wade JD, Bathgate RA, De Meyts P, Nøhr J. Dimerization and negative cooperativity in the relaxin family peptide receptors. Ann NY Acad Sci. 2009;1160:54-9.
52. Roed SN, Orgaard A, Jorgensen R, De Meyts P. Receptor oligomerization in family B1 of G protein-coupled receptors: focus on BRET investigations and the link between GPCR oligomerization and binding cooperativity. Front Endocrin. 2012;3:62. doi: 10.3389/fendo.2012.00062. eCollection.
53. Zoenen M, Urizar E, Swillens S, Vassart G, Costagliola S. Evidence for activity-regulated hormone-binding cooperativity across glycoprotein hormone receptors homomers. Nat Commun. 2012;3:1007. doi: 10.1038/ncomms.
54. Kiselyov VV, Versteyhe S, Gauguin L, De Meyts P. Harmonic oscillator model of the insulin and IGF1 receptors’ allosteric binding and activation. Mol Sys Biol. 2009;5:243. doi: 10.1038/msb.208.78.
55. Ward CW, Lawrence MC, Streltsov VA, Adams TE, McKern NM. The insulin and EGF receptor structures: new insights into ligand-induced receptor activation. Trends Biochem Sci. 2007;32:129-37.
56. Ward CW, Menting JG, Lawrence MC. The insulin receptor changes conformation in unforeseen ways on ligand binding: sharpening the picture of insulin receptor activation. Bioessays. 2013;35:945-54.
57. Huse M, Kuriyan J. The conformational plasticity of protein kinases. Cell. 2002;109:275-82.
58. Ablooglu AJ, Kohanski RA. Activation of the insulin receptor kinase domain changes the rate-determining step of substrate phosphorylation. Biochemistry. 2001;40:504-13.
59. Cobb MH, Sang BC, Gonzales R, Golsmith E, Ellis L. Autophosphorylation activates the soluble cytoplasmic domain of the insulin receptor in an intermolecular reaction. J Biol Chem. 1989;264:18701-6.
60. Zhang X, Gureasko J, Shen K, Cole PA, Kuriyan J. An allosteric mechanism for activation of the kinase domain of epidermal growth factor receptor. Cell. 2006;125:1137-49.
61. Knowles PP, Murray-Rust J, Kjaer S, Scott RP, Hanrahan S, Santoro M, Ibáñez CF, McDonald NQ. Structure and chemical inhibition of the RET tyrosine kinase domain. J Biol Chem. 2006;281:33577-87.
62. Schlessinger J, Lemmon MA. SH2 and PTB domains in tyrosine kinase signaling. Sci STKE. 2003;191:RE12.
63. Pawson T. Specificity in signal transduction: from phosphotyrosine-SH2 domain interactions to complex cellular systems. Cell. 2004;116:191-203.
64. Avruch J. MAP kinase pathways: the first twenty years. Biochem Biophys Acta. 2007;1773:1150-60.
65. Cantley LC. The phosphoinositide 3-kinase pathway. Science. 2002;296:1655-7.
66. Accili D, Arden KC. FoxOs at the crossroads of cellular metabolism, differentiation and transformation. Cell. 2004;117:421-6.
67. Essaghir A, Dif N, Marbehant CY, Coffer PJ, Demoulin JB. The transcription of FoxO genes is stimulated by FoxO3 and repressed by growth factors. J Biol Chem. 2009;284:10334-42.
68. Taniguchi CM, Emmanuelli B, Kahn CR. Critical nodes in signaling pathways: insights into insulin action. Nat Rev Mol Cell Biol. 2006;7:85-96.
69. Taguchi A, White MF. Insulin-like signaling, nutrient homeostasis and lifespan. Ann Rev Physiol. 2008;70:191-212.
70. Boucher J, Kleinridders A, Kahn CR. Insulin receptor signaling in normal and insulin-resistant states. Cold Spring Harb Perspect Biol. 2014;6:a009191.
71. Oda K, Matsuoka Y, Fumahashi A, Kitano H. A comprehensive pathway map of epidermal growth factor receptor signaling. Mol Sys Biol. 2005;1:2005.0010.
72. Siddle K. Molecular basis of signalling specificity of insulin and IGF receptors: neglected corners and recent advances. Front Endocrin. 2012;3:34. doi: 10.3389/fendo.2012.00034.
73. Efstratiadis A. Genetics of mouse growth. Int J Dev Biol. 1998;42:955-76.
74. Lamothe B, Baudry A, Christoffersen CT, De Meyts P, Jami J, Bucchini D, Joshi RL. Insulin receptor-deficient cells as a new tool for dissecting complex interplay in insulin and insulin-like growth factors. FEBS Lett. 1998;426:381-5.
75. Ish-Shalom D, Christoffersen CT, Vorwerk P, Sacerdotti-Sierra N, Shymko RM, De Meyts P. Mitogenic properties of insulin and insulin analogues mediated by the insulin receptor. Diabetologia. 1997;40:S25-31.
76. De Meyts P. Insulin and insulin-like growth factors: the paradox of signaling specificity. Growth Horm IGF Res. 2002;12:81-3.
77. Kim JJ, Accili D. Signaling through IGF-I and insulin receptors: where is the specificity? Growth Horm IGF Res. 2002;12:84-90.
78. Versteyhe S, Klaproth B, Borup R, Palsgaard J, Jensen M, Gray SG, De Meyts P. IGF-I, IGF-II and insulin stimulate different gene expression responses through binding to the IGF-I receptor. Front Endocrin. 2013;4:98. doi: 10.3389/fendo.2013.00098. eCollection.
79. Dittmer F, Ulbrich EJ, Hafner A, Schmahl W, Meister T, Pohlmann R, Von Figura K. Alternative mechanisms for trafficking of lysosomal enzymes in mannose-6-phosphate receptor-deficient mice are cell-type specific. J Cell Sci. 1999;112:1591-7.
80. De Meyts P, Christoffersen CT, Ursø B, Wallach B, Grønskov K, Yakushiji F, Shymko RM. Role of the time factor in signaling specificity: application to mitogenic and metabolic signaling by the insulin and insulin-like growth factor-I receptor tyrosine kinases. Metabolism. 1995;44(10 suppl 4):2-11.
81. Marshall CJ. Specificity of receptor tyrosine kinase signaling: transient versus sustained extracellular signal-regulated kinase activation. Cell. 1995;80:179-85.
82. Santos SD, Verveer PJ, Bastiaens PJ. Growth factor-induced MAPK network topology shapes ERK response determining PC-12 cell fate. Nat Cell Biol. 2007;9:324-30.
83. Schoeberl B, Eichler-Johnsson C, Gilles ED, Mueller G. Computational modeling of the dynamics of the MAP kinase cascade activated by surface and internalized EGF receptors. Nat Biotechnol. 2002;20:370-1.
84. Kitano H. Biological robustness. Nat Rev Genet. 2004;5:826-37.
85. Kholodenko BN. Cell signaling dynamics in time and space. Nat Rev Mol Cell Biol. 2006;17:165-76.
86. Citri A, Yarden Y. EGF-ERBB signalling: towards the systems level. Nat Rev Mol Cell Biol. 2006;7:505-16.
87. Borisov NM, Markevich NI, Hoek JB, Kholodenko BN. Signaling through receptors and scaffolds: independent interactions reduce combinatorial complexity. Biophys J. 2005;89:951-66.
88. Shymko RM, Dumont E, De Meyts P, Dumont J. Timing dependence of insulin-receptor mitogenic versus metabolic signaling: a plausible model based on coincidence of hormone and effector binding. Biochem J. 1999;339:675-83.
89. McGowan CH. Regulation of the eukaryotic cell cycle. Progr Cell Cycle Res. 2003;5:1-4.
90. Morgan DO. Cyclin-dependent kinases: enzymes, clocks and microprocessors. Annu Rev Cell Dev Biol. 1997;13:261-91.
91. Olashaw N, Bagui TK, Pledger WJ. Cell cycle control. A complex issue. Cell Cycle. 2004;3:263-4.
92. Coudreuse D, Nurse P. Driving the cell cycle with a minimal CDK control network. Nature. 2010;468:1075-9.
93. Dupont J, Pierre A, Froment P, Moreau C. The insulin-like growth factor axis in cell cycle progression. Horm Metab Res. 2003;35:740-50.
94. Teng M-H, Bartholomew JC, Bissel MJ. Insulin effects on the cell cycle: analysis of the kinetics of growth parameters in confluent chick cells. Proc Natl Acad Sci U S A. 1976;73:3173-7.
95. Stiles CD, Capone GT, Scher CD, Antoniades HN, Van Wyk JJ, Pledger WJ. Dual control of cell growth by somatomedins and platelet-derived growth factor. Proc Natl Acad Sci U S A. 1979;76:1279-83.
96. O’Keefe EJ, Pledger WJ. A model of cell cycle control: sequential events regulated by growth factors. Mol Cell Endocrinol. 1983;31:167-86.
97. 1 progression and protein modification by SmC/IGF-I. Am J Physiol. 1987;253:C575-9.
98. Jensen M, Palsgaard J, Borup R, De Meyts P, Schäffer L. Activation of the insulin receptor (IR) by insulin and a synthetic peptide has different effects on gene expression in IR-transfected L6 myoblasts. Biochem J. 2008;412:435-45.
99. Svendsen AM, Winge SB, Zimmermann M, Lindvig AB, Warzecha CB, Sajid W, Horne MC, De Meyts P. Down-regulation of cyclin G2 by insulin, IGF-I (insulin like growt factor-I), and X10 (AspB10 insulin): role in mitogenesis. Biochem J. 2014;457:69-77.
100. Horne MC, Goolsby GL, Donaldson KL, Tran D, Neubauer M, Wahl AF. Cyclin G1 and cyclin G2 comprise a new family of cyclins with contrasting tissue-specific and cell-cycle regulated expression. J Biol Chem. 1996;271:6050-61.
101. Horne MC, Donaldson KL, Goolsby GL, Tran D, Mulhelsen M, Hell JW, Wahl AF. Cyclin G2 is upregulated during growth inhibition and B cell antigen receptor-mediated cell cycle arrest. J Biol Chem. 1997;272:12650-61.
102. Bennin DA, Don AS, Brake T, Mckenzie JL, Rosenbaum H, Ortiz L, DePaoli-Roach AA, Horne MC. Cyclin G2 associates with protein phosphatase 2A catalytic and regulatory B subunits in active complexes and induces nuclear aberrations and a G1/S cell cycle arrest. J Biol Chem. 2002;277:27449-67.
103. Le XF, Arachchige-Don AS, Mao W, Horne MC, Bast Jr RC. Roles of human epidermal growth factor receptor 2, c-jun NH2-terminal kinase, phosphoinositide 3-kinase and p70S6 kinase in regulation of cyclin G2 expression in human breast cancer cells. Mol Cancer Ther. 2007;6:2843-57.
104. Jones SM, Kazlaukas A. Growth-factor-dependent mitogenesis requires two distinct phases of signalling. Nat Cell Biol. 2001;3:165-72.
105. Zwang Y, Sas-Chen A, Drier Y, Shay T, Avraham R, Lauriola M, Shema E, Lidor-Nili E, Jacob-Hirsch J, Amariglio N, Lu Y, Mills GB, Rechavi G, Oren M, Domany E, Yarden Y. Two phases of mitogenic signaling unveil roles for p53 and EGR1 in elimination of inconsistent growth signals. Mol Cell. 2011;42:524-35.
106. Jensen M, De Meyts P. Molecular mechanisms of differential signaling from the insulin receptor. Vitam Horm. 2009;80:51-75.
107. Kerr JFR, Wyllie AH, Currie AR. Apoptosis: a basic biological phenomenon with wide-ranging implications in tissue kinetics. Br J Cancer. 1972;26:239-57.
108. Elmore S. Apoptosis: a review of programmed cell death. Toxicol Pathol. 2007;35:495-516.
109. Cory S, Adam JM. The Bc12 family: regulators of the cellular life-or-death switch. Nat Rev Cancer. 2002;2:647-56.
110. Martinvalet D, Zhu P, Lieberman J. Granzyme A induces caspase-independent mitochondrial damage, a required first step for apoptosis. Immunity. 2005;22:355-70.
111. Párrizas M, Saltiel AR, LeRoith D. Insulin-like growth factor-I inhibits apoptosis using the phosphatidylinositol 3'-kinase and mitogen-activated protein kinase pathways. J Biol Chem. 1997;272:154-61.
112. Kooijman R. Regulation of apoptosis by insulin-like growth factor (IGF)-I. Cyt Growth Fact Rev. 2006;17:305-23.
113. Boucher J, Marcotella Y, Bezy O, Mori MA, Kriauciunas K, Kahn CR. A kinase-independent role for unoccupied insulin and IGF-I receptors in the control of apoptosis. Sci Signal. 2010;3(151):ra87. doi: 10.1126/scisignal.2001173.
114. Tseng YH, Ueki K, Kriauciunas KM, Kahn CR. Differential roles of insulin receptor substrates in the anti-apoptotic function of insulin-like growth factor-1 and insulin. J Biol Chem. 2002;277:31601-11.
115. Diaz B, Pimentel B, De Pablo F, De La Rosa EJ. Apoptotic cell death of proliferating neuroepithelial cells in the embryonic retina is prevented by insulin. Eur J Neurosci. 1999;11:1624-32.
116. Bertrand E, Atti A, Cadoret A, L’Allemain G, Robin H, Lascols O, et al. A role for nuclear factor Kappa B in the antiapoptotic function of insulin. J Biol Chem. 1998;273:2931-8.
117. Lee-Kwon W, Park D, Baskar PV, Kole S, Bernier M. Antiapoptotic signalling by the insulin receptor in Chinese hamster ovary cells. Biochemistry. 1998;37:15747-57.
118. Rampalli AM, Zelinka PS. Insulin regulates expression of C-fos and c-jun and suppresses apoptosis of lens epithelial cells. Cell Growth Diff. 1995;6:945-53.
119. Kang S, Song J, Kang H, Kim S, Lee Y, Park D. Insulin can block apoptosis by decreasing oxidative stress via phosphatidylinositol 3-kinase and extracellular signal-regulated protein kinase-dependent signalling pathways in HepG2 cells. Eur J Endocrinol. 2003;148:147-55.
120. Tanaka M, Sawada M, Yoshida S, Hanaoka F, Manurouchi T. Insulin prevents apoptosis of external granular layer neurons in rat cerebellar slice cultures. Neurosci Lett. 1995;199:37-40.
121. Johnson JD, Bernal-Mizzachi E, Alejandro EU, Han Z, Kalynyak TB, Li H, Beith JL, Gross J, Warnock GL, Townsend RR, Permutt MA, Polonski KS. Insulin protects islets from apoptosis via Pdx1 and specific changes in the human islet proteome. Proc Natl Acad Sci U S A. 2006;103:19575-80.
122. Iida KT, Suzuki H, Sone H, Shimano H, Toyoshima H, Yatoh S, Asano T, Okuda Y, Yamada N. Insulin inhibits apoptosis of macrophage cell line, THP-1 cells, via phsphatidylinositol 3-kinase-dependent pathway. Artherioscler Thromb Vasc Biol. 2002;22:380-6.
123. Corcelle EA, Puustinen P, Jäättelä M. Apoptosis and autophagy: targeting autophagy signalling in cancer cells - "trick or treats"? FEBS J. 2009;276:6084-96.
124. Troncoso R, Vicenzio JM, Parra V, Nemchenko A, Kawashima Y, Del Campo A, Toro B, Battiprolu PK, Aranquiz P, Chiong M, Yakar S, Gillette TG, Hill JA, Abel ED, LeRoith D, Levandero S. Energy-preserving effects of IGF-I antagonize starvation-induced cardiac autophagy. Cardiovasc Res. 2012;93:320-9.
125. Danielsen AJ, Mailhe NJ. The EGF/ErbB receptor family and apoptosis. Growth Factors. 2002;20:1-15.
126. Maruyama IN. Mechanisms of activation of receptor tyrosine kinases: monomers or dimers. Cells. 2014;3:304-30. doi:10.3390/cells3020304.