Positive and negative regulation of antigen receptor signaling by the Shc family of protein adapters

Immunological Reviews

Volumn 232, Issue 1, 2009, Pages 115-134

  Finetti, Francesca ^a   Savino, Maria Teresa ^a   Baldari, Cosima T ^a  

^a UNIVERSITY OF SIENA   (Italy)

Author keywords

Adapter; BCR; Protein protein interaction domains; Signal transduction; TCR

Indexed keywords

BREAKPOINT CLUSTER REGION PROTEIN; CD4 ANTIGEN; CHEMOKINE RECEPTOR CXCR4; LYMPHOCYTE ANTIGEN RECEPTOR; MITOGEN ACTIVATED PROTEIN KINASE; MYC PROTEIN; PROTEIN P52; PROTEIN P66; PROTEIN SHC; PROTEIN SHCA; PROTEIN SHCB; PROTEIN SHCC; PROTEIN SHCD; RAC PROTEIN; RAS PROTEIN; STRESS ACTIVATED PROTEIN KINASE; T LYMPHOCYTE RECEPTOR; UNCLASSIFIED DRUG;

APOPTOSIS; AUTOIMMUNITY; B LYMPHOCYTE; B LYMPHOCYTE ACTIVATION; CAENORHABDITIS ELEGANS; CALCIUM HOMEOSTASIS; CELL MATURATION; CELL SURVIVAL; CHEMOTAXIS; DROSOPHILA MELANOGASTER; ENDOCYTOSIS; HEMATOPOIETIC CELL; HUMAN; IMMUNE SYSTEM; MITOCHONDRION; NONHUMAN; PRIORITY JOURNAL; PROTEIN ANALYSIS; PROTEIN EXPRESSION; PROTEIN FAMILY; PROTEIN FUNCTION; PROTEIN PHOSPHORYLATION; PROTEIN PROTEIN INTERACTION; REVIEW; SIGNAL TRANSDUCTION; T LYMPHOCYTE; T LYMPHOCYTE ACTIVATION; TRANSACTIVATION;

ANIMALS; CAENORHABDITIS ELEGANS; DROSOPHILA MELANOGASTER; FEEDBACK, PHYSIOLOGICAL; HUMANS; LYMPHOCYTES; MICE; PROTEIN MULTIMERIZATION; RECEPTORS, ANTIGEN; RECEPTORS, CYTOKINE; SHC SIGNALING ADAPTOR PROTEINS; SIGNAL TRANSDUCTION;

EID: 70350426551     PISSN: 01052896     EISSN: 1600065X     Source Type: Journal    
DOI: 10.1111/j.1600-065X.2009.00826.x     Document Type: Review

References (142)

1. Luzi L, Confalonieri S, Di Fiore PP, Pelicci PG. Evolution of Shc functions from nematode to human. Curr Opin Genet Dev 2000 10 : 668 674.
2. Cattaneo E, Pelicci PG. Emerging roles for SH2/PTB-containing Shc adaptor proteins in the developing mammalian brain. Trends Neurosci 1998 21 : 476 481.
3. Lai KM, Pawson T. The ShcA phosphotyrosine docking protein sensitizes cardiovascular signaling in the mouse embryo. Genes Dev 2000 14 : 1132 1145.
4. Migliaccio E, et al. The p66Shc adaptor protein controls oxidative stress response and life span in mammals. Nature 1999 402 : 309 313.
5. Luschnig S, Krauss J, Bohmann K, Desjeux I, Nusslein-Volhard C. The Drosophila SHC adaptor protein is required for signaling by a subset of receptor tyrosine kinases. Mol Cell 2000 5 : 231 241.
6. Bianco A, et al. Two distinct modes of guidance signalling during collective migration of border cells. Nature 2007 448 : 362 365.
7. Neumann-Haefelin E, Qi W, Finkbeiner E, Walz G, Baumeister R, Hertweck M. SHC-1/p52Shc targets the insulin/IGF-1 and JNK signaling pathways to modulate life span and stress response in C. elegans. Genes Dev 2008 22 : 2721 2735.
8. O'Bryan JP, Songyang Z, Cantley L, Der CJ, Pawson T. A mammalian adaptor protein with conserved Src homology 2 and phosphotyrosine-binding domains is related to Shc and is specifically expressed in the brain. Proc Natl Acad Sci USA 1996 93 : 2729 2734.
9. Nakamura T, Muraoka S, Sanokawa R, Mori N. N-Shc and Sck, two neuronally expressed Shc adapter homologs. Their differential regional expression in the brain and roles in neurotrophin and Src signaling. J Biol Chem 1998 273 : 6960 6967.
10. Pelicci G, et al. A family of Shc related proteins with conserved PTB, CH1 and SH2 regions. Oncogene 1996 13 : 633 641.
11. Conti L, De Fraja C, Gulisano M, Migliaccio E, Govoni S, Cattaneo E. Expression and activation of SH2/PTB-containing ShcA adaptor protein reflects the pattern of neurogenesis in the mammalian brain. Proc Natl Acad Sci USA 1997 94 : 8185 8190.
12. Sakai R, Henderson JT, O'Bryan JP, Elia AJ, Saxton TM, Pawson T. The mammalian ShcB and ShcC phosphotyrosine docking proteins function in the maturation of sensory and sympathetic neurons. Neuron 2000 28 : 819 833.
13. Troglio F, et al. The Rai (Shc C) adaptor protein regulates the neuronal stress response and protects against cerebral ischemia. Proc Natl Acad Sci USA 2004 101 : 15476 15481.
14. Fagiani E, et al. RaLP, a new member of the Src homology and collagen family, regulates cell migration and tumor growth of metastatic melanomas. Cancer Res 2007 67 : 3064 3073.
15. Jones N, et al. Analysis of a Shc family adaptor protein, ShcD/Shc4, that associates with muscle-specific kinase. Mol Cell Biol 2007 27 : 4759 4773.
16. Ravichandran KS. Signaling via Shc family adapter proteins. Oncogene 2001 20 : 6322 6330.
17. Audero E, et al. Adaptor ShcA protein binds tyrosine kinase Tie2 receptor and regulates migration and sprouting but not survival of endothelial cells. J Biol Chem 2004 279 : 13224 13233.
18. Radhakrishnan Y, Maile LA, Ling Y, Graves LM, Clemmons DR. Insulin-like growth factor-I stimulates Shc-dependent phosphatidylinositol 3-kinase activation via Grb2-associated p85 in vascular smooth muscle cells. J Biol Chem 2008 283 : 16320 16331.
19. Medina DL, Sciarretta C, Calella AM, Von Bohlen Und Halbach O, Unsicker K, Minichiello L. TrkB regulates neocortex formation through the Shc/PLCgamma-mediated control of neuronal migration. EMBO J 2004 23 : 3803 3814.
20. Zhang L, Lorenz U, Ravichandran KS. Role of Shc in T-cell development and function. Immunol Rev 2003 191 : 183 195.
21. Hardy WR, et al. Combinatorial ShcA docking interactions support diversity in tissue morphogenesis. Science 2007 317 : 251 256.
22. Zhang L, Camerini V, Bender TP, Ravichandran KS. A nonredundant role for the adapter protein Shc in thymic T cell development. Nat Immunol 2002 3 : 749 755.
23. Swan KA, et al. Involvement of p21ras distinguishes positive and negative selection in thymocytes. EMBO J 1995 14 : 276 285.
24. Ravichandran KS, Lee KK, Songyang Z, Cantley LC, Burn P, Burakoff SJ. Interaction of Shc with the zeta chain of the T cell receptor upon T cell activation. Science 1993 262 : 902 905.
25. Pacini S, et al. Tyrosine 474 of ZAP-70 is required for association with the Shc adaptor and for T-cell antigen receptor-dependent gene activation. J Biol Chem 1998 273 : 20487 20493.
26. Walk SF, March ME, Ravichandran KS. Roles of Lck, Syk and ZAP-70 tyrosine kinases in TCR-mediated phosphorylation of the adapter protein Shc. Eur J Immunol 1998 28 : 2265 2275.
27. Baldari CT, Milia E, Di Somma MM, Baldoni F, Valitutti S, Telford JL. Distinct signaling properties identify functionally different CD4 epitopes. Eur J Immunol 1995 25 : 1843 1850.
28. Marengere LE, Waterhouse P, Duncan GS, Mittrucker HW, Feng GS, Mak TW. Regulation of T cell receptor signaling by tyrosine phosphatase SYP association with CTLA-4. Science 1996 272 : 1170 1173.
29. Stefanova I, Hemmer B, Vergelli M, Martin R, Biddison WE, Germain RN. TCR ligand discrimination is enforced by competing ERK positive and SHP-1 negative feedback pathways. Nat Immunol 2003 4 : 248 254.
30. Milia E, et al. The aminoterminal phosphotyrosine binding domain of Shc associates with ZAP-70 and mediates TCR dependent gene activation. Oncogene 1996 13 : 767 775.
31. Plyte S, et al. Constitutive activation of the Ras/MAP kinase pathway and enhanced TCR signaling by targeting the Shc adaptor to membrane rafts. Oncogene 2000 19 : 1529 1537.
32. Valensin S, et al. F-actin dynamics control segregation of the TCR signaling cascade to clustered lipid rafts. Eur J Immunol 2002 32 : 435 446.
33. Bini L, et al. Extensive temporally regulated reorganization of the lipid raft proteome following T-cell antigen receptor triggering. Biochem J 2003 369 : 301 309.
34. Groysman M, Hornstein I, Alcover A, Katzav S. Vav1 and Ly-GDI two regulators of Rho GTPases, function cooperatively as signal transducers in T cell antigen receptor-induced pathways. J Biol Chem 2002 277 : 50121 50130.
35. Zhou MM, et al. Structure and ligand recognition of the phosphotyrosine binding domain of Shc. Nature 1995 378 : 584 592.
36. Rameh LE, et al. A comparative analysis of the phosphoinositide binding specificity of pleckstrin homology domains. J Biol Chem 1997 272 : 22059 22066.
37. Ravichandran KS, et al. Evidence for a requirement for both phospholipid and phosphotyrosine binding via the Shc phosphotyrosine-binding domain in vivo. Mol Cell Biol 1997 17 : 5540 5549.
38. Zhou MM, et al. Solution structure of the Shc SH2 domain complexed with a tyrosine-phosphorylated peptide from the T-cell receptor. Proc Natl Acad Sci USA 1995 92 : 7784 7788.
39. Labadia ME, Ingraham RH, Schembri-King J, Morelock MM, Jakes S. Binding affinities of the SH2 domains of ZAP-70, p56lck and Shc to the zeta chain ITAMs of the T-cell receptor determined by surface plasmon resonance. J Leukoc Biol 1996 59 : 740 746.
40. Zenner G, Vorherr T, Mustelin T, Burn P. Differential and multiple binding of signal transducing molecules to the ITAMs of the TCR-zeta chain. J Cell Biochem 1996 63 : 94 103.
41. Fukushima A, Hatanaka Y, Chang JW, Takamatsu M, Singh N, Iwashima M. Lck couples Shc to TCR signaling. Cell Signal 2006 18 : 1182 1189.
42. Baldari CT, et al. Inhibition of CD4/p56lck signaling by a dominant negative mutant of the Shc adaptor protein. Oncogene 1995 10 : 1141 1147.
43. Pratt JC, van den Brink MR, Igras VE, Walk SF, Ravichandran KS, Burakoff SJ. Requirement for Shc in TCR-mediated activation of a T cell hybridoma. J Immunol 1999 163 : 2586 2591.
44. Patrussi L, et al. Cooperation and selectivity of the two Grb2 binding sites of p52Shc in T-cell antigen receptor signaling to Ras family GTPases and Myc-dependent survival. Oncogene 2005 24 : 2218 2228.
45. Ravichandran KS, Lorenz U, Shoelson SE, Burakoff SJ. Interaction of Shc with Grb2 regulates the Grb2 association with mSOS. Ann NY Acad Sci 1995 766 : 202 203.
46. Pacini S, Valensin S, Telford JL, Ladbury J, Baldari CT. Temporally regulated assembly of a dynamic signaling complex associated with the activated TCR. Eur J Immunol 2000 30 : 2620 2631.
47. Iwashima M, et al. Genetic evidence for Shc requirement in TCR-induced c-Rel nuclear translocation and IL-2 expression. Proc Natl Acad Sci USA 2002 99 : 4544 4549.
48. van der Geer P, et al. Identification of residues that control specific binding of the Shc phosphotyrosine-binding domain to phosphotyrosine sites. Proc Natl Acad Sci USA 1996 93 : 963 968.
49. Springett GM, Kawasaki H, Spriggs DR. Non-kinase second-messenger signaling: new pathways with new promise. BioEssays 2004 26 : 730 738.
50. Roose JP, Mollenauer M, Ho M, Kurosaki T, Weiss A. Unusual interplay of two types of Ras activators, RasGRP and SOS, establishes sensitive and robust Ras activation in lymphocytes. Mol Cell Biol 2007 27 : 2732 2745.
51. Das J, et al. Digital signaling and hysteresis characterize ras activation in lymphoid cells. Cell 2009 136 : 337 351.
52. Mariathasan S, Zakarian A, Bouchard D, Michie AM, Zuniga-Pflucker JC, Ohashi PS. Duration and strength of extracellular signal-regulated kinase signals are altered during positive versus negative thymocyte selection. J Immunol 2001 167 : 4966 4973.
53. McNeil LK, Starr TK, Hogquist KA. A requirement for sustained ERK signaling during thymocyte positive selection in vivo. Proc Natl Acad Sci USA 2005 102 : 13574 13579.
54. Koretzky GA. The role of Grb2-associated proteins in T-cell activation. Immunol Today 1997 18 : 401 406.
55. Bustelo XR. Regulatory and signaling properties of the Vav family. Mol Cell Biol 2000 20 : 1461 1477.
56. Nimnual AS, Yatsula BA, Bar-Sagi D. Coupling of Ras and Rac guanosine triphosphatases through the Ras exchanger Sos. Science 1998 279 : 560 563.
57. Cantrell DA. GTPases and T cell activation. Immunol Rev 2003 192 : 122 130.
58. Barberis L, et al. Distinct roles of the adaptor protein Shc and focal adhesion kinase in integrin signaling to ERK. J Biol Chem 2000 275 : 36532 36540.
59. Thomas D, Patterson SD, Bradshaw RA. Src homologous and collagen (Shc) protein binds to F-actin and translocates to the cytoskeleton upon nerve growth factor stimulation in PC12 cells. J Biol Chem 1995 270 : 28924 28931.
60. Gotoh N, Tojo A, Shibuya M. A novel pathway from phosphorylation of tyrosine residues 239/240 of Shc, contributing to suppress apoptosis by IL-3. EMBO J 1996 15 : 6197 6204.
61. Gotoh N, Toyoda M, Shibuya M. Tyrosine phosphorylation sites at amino acids 239 and 240 of Shc are involved in epidermal growth factor-induced mitogenic signaling that is distinct from Ras/mitogen-activated protein kinase activation. Mol Cell Biol 1997 17 : 1824 1831.
62. Lord JD, McIntosh BC, Greenberg PD, Nelson BH. The IL-2 receptor promotes proliferation, bcl-2 and bcl-x induction, but not cell viability through the adapter molecule Shc. J Immunol 1998 161 : 4627 4633.
63. Atwal JK, Massie B, Miller FD, Kaplan DR. The TrkB-Shc site signals neuronal survival and local axon growth via MEK and P13-kinase. Neuron 2000 27 : 265 277.
64. Besset V, Scott RP, Ibanez CF. Signaling complexes and protein-protein interactions involved in the activation of the Ras and phosphatidylinositol 3-kinase pathways by the c-Ret receptor tyrosine kinase. J Biol Chem 2000 275 : 39159 39166.
65. Matter ML, Ruoslahti E. A signaling pathway from the alpha5beta1 and alpha(v)beta3 integrins that elevates bcl-2 transcription. J Biol Chem 2001 276 : 27757 27763.
66. Kinoshita T, Yokota T, Arai K, Miyajima A. Regulation of Bcl-2 expression by oncogenic Ras protein in hematopoietic cells. Oncogene 1995 10 : 2207 2212.
67. Patrussi L, Baldari CT. Intracellular mediators of CXCR4-dependent signaling in T cells. Immunol Lett 2008 115 : 75 82.
68. Patrussi L, et al. p52Shc is required for CXCR4-dependent signaling and chemotaxis in T cells. Blood 2007 110 : 1730 1738.
69. Vang T, et al. Activation of the COOH-terminal Src kinase (Csk) by cAMP-dependent protein kinase inhibits signaling through the T cell receptor. J Exp Med 2001 193 : 497 507.
70. Lotti LV, et al. Sch proteins are localized on endoplasmic reticulum membranes and are redistributed after tyrosine kinase receptor activation. Mol Cell Biol 1996 16 : 1946 1954.
71. Baron V, Alengrin F, Van Obberghen E. Dynamin associates with Src-homology collagen (Shc) and becomes tyrosine phosphorylated in response to insulin. Endocrinology 1998 139 : 3034 3037.
72. Okabayashi Y, et al. Interaction of Shc with adaptor protein adaptins. J Biol Chem 1996 271 : 5265 5269.
73. Ceresa BP, Schmid SL. Regulation of signal transduction by endocytosis. Curr Opin Cell Biol 2000 12 : 204 210.
74. Jiang X, Sorkin A. Coordinated traffic of Grb2 and Ras during epidermal growth factor receptor endocytosis visualized in living cells. Mol Biol Cell 2002 13 : 1522 1535.
75. Burke P, Schooler K, Wiley HS. Regulation of epidermal growth factor receptor signaling by endocytosis and intracellular trafficking. Mol Biol Cell 2001 12 : 1897 1910.
76. Daniels MA, et al. Thymic selection threshold defined by compartmentalization of Ras/MAPK signalling. Nature 2006 444 : 724 729.
77. Rozengurt E. Mitogenic signaling pathways induced by G protein-coupled receptors. J Cell Physiol 2007 213 : 589 602.
78. Kumar A, et al. CXCR4 physically associates with the T cell receptor to signal in T cells. Immunity 2006 25 : 213 224.
79. Nagai K, Takata M, Yamamura H, Kurosaki T. Tyrosine phosphorylation of Shc is mediated through Lyn and Syk in B cell receptor signaling. J Biol Chem 1995 270 : 6824 6829.
80. Smit L, de Vries-Smits AM, Bos JL, Borst J. B cell antigen receptor stimulation induces formation of a Shc-Grb2 complex containing multiple tyrosine-phosphorylated proteins. J Biol Chem 1994 269 : 20209 20212.
81. Saxton TM, van Oostveen I, Bowtell D, Aebersold R, Gold MR. B cell antigen receptor cross-linking induces phosphorylation of the p21ras oncoprotein activators SHC and mSOS1 as well as assembly of complexes containing SHC, GRB-2, mSOS1, and a 145-kDa tyrosine-phosphorylated protein. J Immunol 1994 153 : 623 636.
82. Harmer SL, DeFranco AL. Shc contains two Grb2 binding sites needed for efficient formation of complexes with SOS in B lymphocytes. Mol Cell Biol 1997 17 : 4087 4095.
83. Baumann G, Maier D, Freuler F, Tschopp C, Baudisch K, Wienands J. In vitro characterization of major ligands for Src homology 2 domains derived from protein tyrosine kinases, from the adaptor protein SHC and from GTPase-activating protein in Ramos B cells. Eur J Immunol 1994 24 : 1799 1807.
84. D'Ambrosio D, Hippen KL, Cambier JC. Distinct mechanisms mediate SHC association with the activated and resting B cell antigen receptor. Eur J Immunol 1996 26 : 1960 1965.
85. Davidson D, Veillette A. PTP-PEST, a scaffold protein tyrosine phosphatase, negatively regulates lymphocyte activation by targeting a unique set of substrates. EMBO J 2001 20 : 3414 3426.
86. Chen L, Juszczynski P, Takeyama K, Aguiar RC, Shipp MA. Protein tyrosine phosphatase receptor-type O truncated (PTPROt) regulates SYK phosphorylation, proximal B-cell-receptor signaling, and cellular proliferation. Blood 2006 108 : 3428 3433.
87. Panchamoorthy G, et al. p120cbl is a major substrate of tyrosine phosphorylation upon B cell antigen receptor stimulation and interacts in vivo with Fyn and Syk tyrosine kinases, Grb2 and Shc adaptors, and the p85 subunit of phosphatidylinositol 3-kinase. J Biol Chem 1996 271 : 3187 3194.
88. Tridandapani S, Kelley T, Pradhan M, Cooney D, Justement LB, Coggeshall KM. Recruitment and phosphorylation of SH2-containing inositol phosphatase and Shc to the B-cell Fc gamma immunoreceptor tyrosine-based inhibition motif peptide motif. Mol Cell Biol 1997 17 : 4305 4311.
89. Tridandapani S, Chacko GW, Van Brocklyn JR, Coggeshall KM. Negative signaling in B cells causes reduced Ras activity by reducing Shc-Grb2 interactions. J Immunol 1997 158 : 1125 1132.
90. Ingham RJ, et al. Tyrosine phosphorylation of Shc in response to B cell antigen receptor engagement depends on the SHIP inositol phosphatase. J Immunol 1999 163 : 5891 5895.
91. Coggeshall KM. Inhibitory signaling by B cell Fc gamma RIIb. Curr Opin Immunol 1998 10 : 306 312.
92. Pelicci G, et al. A novel transforming protein (SHC) with an SH2 domain is implicated in mitogenic signal transduction. Cell 1992 70 : 93 104.
93. Lee MS, et al. p66Shc protein is upregulated by steroid hormones in hormone-sensitive cancer cells and in primary prostate carcinomas. Int J Cancer 2004 108 : 672 678.
94. Pacini S, et al. p66SHC promotes apoptosis and antagonizes mitogenic signaling in T cells. Mol Cell Biol 2004 24 : 1747 1757.
95. Pagnin E, Fadini G, de Toni R, Tiengo A, Calo L, Avogaro A. Diabetes induces p66Shc gene expression in human peripheral blood mononuclear cells: relationship to oxidative stress. J Clin Endocrinol Metab 2005 90 : 1130 1136.
96. Park YJ, et al. p66Shc expression in proliferating thyroid cells is regulated by thyrotropin receptor signaling. Endocrinology 2005 146 : 2473 2480.
97. Carraro F, Pucci A, Pellegrini M, Pelicci PG, Baldari CT, Naldini A. p66Shc is involved in promoting HIF-1alpha accumulation and cell death in hypoxic T cells. J Cell Physiol 2007 211 : 439 447.
98. Sansone P, et al. p66Shc/Notch-3 interplay controls self-renewal and hypoxia survival in human stem/progenitor cells of the mammary gland expanded in vitro as mammospheres. Stem Cells 2007 25 : 807 815.
99. Ventura A, Luzi L, Pacini S, Baldari CT, Pelicci PG. The p66Shc longevity gene is silenced through epigenetic modifications of an alternative promoter. J Biol Chem 2002 277 : 22370 22376.
100. Migliaccio E, et al. Opposite effects of the p52Shc/p46Shc and p66Shc splicing isoforms on the EGF receptor-MAP kinase-fos signalling pathway. EMBO J 1997 16 : 706 716.
101. Okada S, Kao AW, Ceresa BP, Blaikie P, Margolis B, Pessin JE. The 66-kDa Shc isoform is a negative regulator of the epidermal growth factor-stimulated mitogen-activated protein kinase pathway. J Biol Chem 1997 272 : 28042 28049.
102. Khanday FA, et al. Sos-mediated activation of rac1 by p66Shc. J Cell Biol 2006 172 : 817 822.
103. Ma Z, Myers DP, Wu RF, Nwariaku FE, Terada LS. p66Shc mediates anoikis through RhoA. J Cell Biol 2007 179 : 23 31.
104. Nemoto S, Finkel T. Redox regulation of forkhead proteins through a p66Shc-dependent signaling pathway. Science 2002 295 : 2450 2452.
105. Orsini F, et al. The life span determinant p66Shc localizes to mitochondria where it associates with mitochondrial heat shock protein 70 and regulates trans-membrane potential. J Biol Chem 2004 279 : 25689 25695.
106. Trinei M, et al. A p53-p66Shc signalling pathway controls intracellular redox status, levels of oxidation-damaged DNA and oxidative stress-induced apoptosis. Oncogene 2002 21 : 3872 3878.
107. Giorgio M, et al. Electron transfer between cytochrome c and p66Shc generates reactive oxygen species that trigger mitochondrial apoptosis. Cell 2005 122 : 221 233.
108. Gertz M, Fischer F, Wolters D, Steegborn C. Activation of the lifespan regulator p66Shc through reversible disulfide bond formation. Proc Natl Acad Sci USA 2008 105 : 5705 5709.
109. Rasola A, Bernardi P. The mitochondrial permeability transition pore and its involvement in cell death and in disease pathogenesis. Apoptosis 2007 12 : 815 833.
110. Pinton P, et al. Protein kinase C beta and prolyl isomerase 1 regulate mitochondrial effects of the life-span determinant p66Shc. Science 2007 315 : 659 663.
111. Arany I, Faisal A, Nagamine Y, Safirstein RL. p66Shc inhibits pro-survival epidermal growth factor receptor/ERK signaling during severe oxidative stress in mouse renal proximal tubule cells. J Biol Chem 2008 283 : 6110 6117.
112. Napoli C, et al. Deletion of the p66Shc longevity gene reduces systemic and tissue oxidative stress, vascular cell apoptosis, and early atherogenesis in mice fed a high-fat diet. Proc Natl Acad Sci USA 2003 100 : 2112 2116.
113. Francia P, et al. Deletion of p66Shc gene protects against age-related endothelial dysfunction. Circulation 2004 110 : 2889 2895.
114. Camici GG, et al. Genetic deletion of p66(Shc) adaptor protein prevents hyperglycemia-induced endothelial dysfunction and oxidative stress. Proc Natl Acad Sci USA 2007 104 : 5217 5222.
115. Graiani G, et al. Genetic deletion of the p66Shc adaptor protein protects from angiotensin II-induced myocardial damage. Hypertension 2005 46 : 433 440.
116. Menini S, et al. Deletion of p66Shc longevity gene protects against experimental diabetic glomerulopathy by preventing diabetes-induced oxidative stress. Diabetes 2006 55 : 1642 1650.
117. Martin-Padura I, et al. p66Shc deletion confers vascular protection in advanced atherosclerosis in hypercholesterolemic apolipoprotein E knockout mice. Endothelium 2008 15 : 276 287.
118. Finetti F, et al. The proapoptotic and antimitogenic protein p66SHC acts as a negative regulator of lymphocyte activation and autoimmunity. Blood 2008 111 : 5017 5027.
119. Pezzicoli A, Ulivieri C, Capitani N, Ventura A, Pelicci P, Baldari CT. Expression in T-cells of the proapoptotic protein p66SHC is controlled by promoter demethylation. Biochem Biophys Res Commun 2006 349 : 322 328.
120. Xie Y, Hung MC. p66Shc isoform down-regulated and not required for HER-2/neu signaling pathway in human breast cancer cell lines with HER-2/neu overexpression. Biochem Biophys Res Commun 1996 221 : 140 145.
121. Stevenson LE, Frackelton AR Jr. Constitutively tyrosine phosphorylated p52 Shc in breast cancer cells: correlation with ErbB2 and p66 Shc expression. Breast Cancer Res Treat 1998 49 : 119 128.
122. Kim CS, et al. p53 impairs endothelium-dependent vasomotor function through transcriptional upregulation of p66Shc. Circ Res 2008 103 : 1441 1450.
123. Pellegrini M, et al. p66SHC promotes T cell apoptosis by inducing mitochondrial dysfunction and impaired Ca2+ homeostasis. Cell Death Differ 2007 14 : 338 347.
124. 2+ as a key regulator of cell life and death. Cell Death Differ 2007 14 : 1267 1274.
125. Foschi M, Franchi F, Han J, La Villa G, Sorokin A. Endothelin-1 induces serine phosphorylation of the adaptor protein p66Shc and its association with 14-3-3 protein in glomerular mesangial cells. J Biol Chem 2001 276 : 26640 26647.
126. Van Der Hoeven PC, Van Der Wal JC, Ruurs P, Van Dijk MC, Van Blitterswijk J. 14-3-3 isotypes facilitate coupling of protein kinase C-zeta to Raf-1: negative regulation by 14-3-3 phosphorylation. Biochem J 2000 345 : 297 306.
127. Sharara LI, Andersson A, Guy-Grand D, Fischer A, DiSanto JP. Deregulated TCR alpha beta T cell population provokes extramedullary hematopoiesis in mice deficient in the common gamma chain. Eur J Immunol 1997 27 : 990 998.
128. He TC, Jiang N, Zhuang H, Wojchowski DM. Erythropoietin-induced recruitment of Shc via a receptor phosphotyrosine-independent, Jak2-associated pathway. J Biol Chem 1995 270 : 11055 11061.
129. Matsuguchi T, et al. Shc phosphorylation in myeloid cells is regulated by granulocyte macrophage colony-stimulating factor, interleukin-3, and steel factor and is constitutively increased by p210BCR/ABL. J Biol Chem 1994 269 : 5016 5021.
130. Park RK, Izadi KD, Deo YM, Durden DL. Role of Src in the modulation of multiple adaptor proteins in FcalphaRI oxidant signaling. Blood 1999 94 : 2112 2120.
131. Jabril-Cuenod B, et al. Syk-dependent phosphorylation of Shc. A potential link between FcepsilonRI and the Ras/mitogen-activated protein kinase signaling pathway through SOS and Grb2. J Biol Chem 1996 271 : 16268 16272.
132. Kimura T, Kihara H, Bhattacharyya S, Sakamoto H, Appella E, Siraganian RP. Downstream signaling molecules bind to different phosphorylated immunoreceptor tyrosine-based activation motif (ITAM) peptides of the high affinity IgE receptor. J Biol Chem 1996 271 : 27962 27968.
133. Leitges M, et al. Protein kinase C-delta is a negative regulator of antigen-induced mast cell degranulation. Mol Cell Biol 2002 22 : 3970 3980.
134. Nakamura T, Sanokawa R, Sasaki Y, Ayusawa D, Oishi M, Mori N. N-Shc: a neural-specific adapter molecule that mediates signaling from neurotrophin/Trk to Ras/MAPK pathway. Oncogene 1996 13 : 1111 1121.
135. Conti L, et al. Shc signaling in differentiating neural progenitor cells. Nat Neurosci 2001 4 : 579 586.
136. Nakamura T, Komiya M, Gotoh N, Koizumi S, Shibuya M, Mori N. Discrimination between phosphotyrosine-mediated signaling properties of conventional and neuronal Shc adapter molecules. Oncogene 2002 21 : 22 31.
137. Pelicci G, et al. The neuron-specific Rai (ShcC) adaptor protein inhibits apoptosis by coupling Ret to the phosphatidylinositol 3-kinase/Akt signaling pathway. Mol Cell Biol 2002 22 : 7351 7363.
138. Liu HY, Meakin SO. ShcB and ShcC activation by the Trk family of receptor tyrosine kinases. J Biol Chem 2002 277 : 26046 26056.
139. Nakazawa T, Nakano I, Sato M, Nakamura T, Tamai M, Mori N. Comparative expression profiles of Trk receptors and Shc-related phosphotyrosine adapters during retinal development: potential roles of N-Shc/ShcC in brain-derived neurotrophic factor signal transduction and modulation. J Neurosci Res 2002 68 : 668 680.
140. Villanacci V, et al. Expression of the Rai (Shc C) adaptor protein in the human enteric nervous system. Neurogastroenterol Motil 2008 20 : 206 212.
141. Savino MT, et al. Rai acts as a negative regulator of autoimmunity by inhibiting antigen receptor signaling and lymphocyte activation. J Immunol 2009 182 : 301 308.
142. Veillette A, Dong Z, Latour S. Consequence of the SLAM-SAP signaling pathway in innate-like and conventional lymphocytes. Immunity 2007 27 : 698 710.