• 1
    Cohen P (2006) The twentieth century struggle to decipher insulin signalling. Nat Rev Mol Cell Biol 7, 867873.
  • 2
    Taniguchi CM, Emanuelli B & Kahn CR (2006) Critical nodes in signalling pathways: insights into insulin action. Nat Rev Mol Cell Biol 7, 8596.
  • 3
    Youngren JF (2007) Regulation of insulin receptor function. Cell Mol Life Sci 64, 873891.
  • 4
    Siddle K (2012) Molecular basis of signaling specificity of insulin and IGF receptors: neglected corners and recent advances. Front Endocrinol (Lausanne) 3, 34.
  • 5
    Lim MA, Riedel H & Liu F (2004) Grb10: more than a simple adaptor protein. Front Biosci 9, 387403.
  • 6
    Riedel H (2004) Grb10 exceeding the boundaries of a common signaling adapter. Front Biosci 9, 603618.
  • 7
    Cariou B, Bereziat V, Moncoq K, Kasus-Jacobi A, Perdereau D, Le Marcis V & Burnol AF (2004) Regulation and functional roles of Grb14. Front Biosci 9, 16261636.
  • 8
    Holt LJ & Siddle K (2005) Grb10 and Grb14: enigmatic regulators of insulin action –and more? Biochem J 388, 393406.
  • 9
    Shen TL & Guan JL (2004) Grb7 in intracellular signaling and its role in cell regulation. Front Biosci 9, 192200.
  • 10
    Maures TJ, Kurzer JH & Carter-Su C (2007) SH2B1 (SH2–B) and JAK2: a multifunctional adaptor protein and kinase made for each other. Trends Endocrinol Metab 18, 3845.
  • 11
    Stein EG, Ghirlando R & Hubbard SR (2003) Structural basis for dimerization of the Grb10 Src homology 2 domain. Implications for ligand specificity. J Biol Chem 278, 1325713264.
  • 12
    Nouaille S, Blanquart C, Zilberfarb V, Boute N, Perdereau D, Burnol AF & Issad T (2006) Interaction between the insulin receptor and Grb14: a dynamic study in living cells using BRET. Biochem Pharmacol 72, 13551366.
  • 13
    Depetris RS, Hu J, Gimpelevich I, Holt LJ, Daly RJ & Hubbard SR (2005) Structural basis for inhibition of the insulin receptor by the adaptor protein Grb14. Mol Cell 20, 325333.
  • 14
    Depetris RS, Wu J & Hubbard SR (2009) Structural and functional studies of the Ras-associating and pleckstrin-homology domains of Grb10 and Grb14. Nat Struct Mol Biol 16, 833839.
  • 15
    Dhe-Paganon S, Werner ED, Nishi M, Hansen L, Chi YI & Shoelson SE (2004) A phenylalanine zipper mediates APS dimerization. Nat Struct Mol Biol 11, 968974.
  • 16
    Nishi M, Werner ED, Oh BC, Frantz JD, Dhe-Paganon S, Hansen L, Lee J & Shoelson SE (2005) Kinase activation through dimerization by human SH2–B. Mol Cell Biol 25, 26072621.
  • 17
    Hu J, Liu J, Ghirlando R, Saltiel AR & Hubbard SR (2003) Structural basis for recruitment of the adaptor protein APS to the activated insulin receptor. Mol Cell 12, 13791389.
  • 18
    Hu J & Hubbard SR (2006) Structural basis for phosphotyrosine recognition by the Src homology–2 domains of the adapter proteins SH2–B and APS. J Mol Biol 361, 6979.
  • 19
    Moncoq K, Broutin I, Larue V, Perdereau D, Cailliau K, Browaeys-Poly E, Burnol AF & Ducruix A (2003) The PIR domain of Grb14 is an intrinsically unstructured protein: implication in insulin signaling. FEBS Lett 554, 240246.
  • 20
    Shen TL, Han DC & Guan JL (2002) Association of Grb7 with phosphoinositides and its role in the regulation of cell migration. J Biol Chem 277, 2906929077.
  • 21
    Rajala RV, Chan MD & Rajala A (2005) Lipid–protein interactions of growth factor receptor-bound protein 14 in insulin receptor signaling. Biochemistry 44, 1546115471.
  • 22
    Rodriguez-Viciana P, Sabatier C & McCormick F (2004) Signaling specificity by Ras family GTPases is determined by the full spectrum of effectors they regulate. Mol Cell Biol 24, 49434954.
  • 23
    Browaeys-Poly E, Blanquart C, Perdereau D, Antoine AF, Goenaga D, Luzy JP, Chen H, Garbay C, Issad T, Cailliau K et al. (2010) Grb14 inhibits FGF receptor signaling through the regulation of PLCγ recruitment and activation. FEBS Lett 584, 43834388.
  • 24
    Jones N, Master Z, Jones J, Bouchard D, Gunji Y, Sasaki H, Daly R, Alitalo K & Dumont DJ (1999) Identification of Tek/Tie2 binding partners. Binding to a multifunctional docking site mediates cell survival and migration. J Biol Chem 274, 3089630905.
  • 25
    Stein D, Wu J, Fuqua SA, Roonprapunt C, Yajnik V, D'Eustachio P, Moskow JJ, Buchberg AM, Osborne CK & Margolis B (1994) The SH2 domain protein GRB–7 is co-amplified, overexpressed and in a tight complex with HER2 in breast cancer. EMBO J 13, 13311340.
  • 26
    Chu PY, Huang LY, Hsu CH, Liang CC, Guan JL, Hung TH & Shen TL (2009) Tyrosine phosphorylation of growth factor receptor-bound protein–7 by focal adhesion kinase in the regulation of cell migration, proliferation, and tumorigenesis. J Biol Chem 284, 2021520226.
  • 27
    Frantz JD, Giorgetti-Peraldi S, Ottinger EA & Shoelson SE (1997) Human GRB–IRβ/GRB10. Splice variants of an insulin and growth factor receptor-binding protein with PH and SH2 domains. J Biol Chem 272, 26592667.
  • 28
    Langlais P, Dong LQ, Hu D & Liu F (2000) Identification of Grb10 as a direct substrate for members of the Src tyrosine kinase family. Oncogene 19, 28952903.
  • 29
    Mano H, Ohya K, Miyazato A, Yamashita Y, Ogawa W, Inazawa J, Ikeda U, Shimada K, Hatake K, Kasuga M et al. (1998) Grb10/GrbIR as an in vivo substrate of Tec tyrosine kinase. Genes Cells 3, 431441.
  • 30
    Sturk C & Dumont DJ (2010) Tyrosine phosphorylation of Grb14 by Tie2. Cell Commun Signal 8, 30.
  • 31
    Basavarajappa DK, Gupta VK, Dighe R, Rajala A & Rajala RV (2011) Phosphorylated Grb14 is an endogenous inhibitor of retinal protein tyrosine phosphatase 1B, and light-dependent activation of Src phosphorylates Grb14. Mol Cell Biol 31, 39753987.
  • 32
    Cailliau K, Le Marcis V, Bereziat V, Perdereau D, Cariou B, Vilain JP, Burnol AF & Browaeys-Poly E (2003) Inhibition of FGF receptor signalling in Xenopus oocytes: differential effect of Grb7, Grb10 and Grb14. FEBS Lett 548, 4348.
  • 33
    Wang J, Dai H, Yousaf N, Moussaif M, Deng Y, Boufelliga A, Swamy OR, Leone ME & Riedel H (1999) Grb10, a positive, stimulatory signaling adapter in platelet-derived growth factor BB-, insulin-like growth factor I-, and insulin-mediated mitogenesis. Mol Cell Biol 19, 62176228.
  • 34
    Balogh K, Asa SL, Zheng L, Cassol C, Cheng S & Ezzat S (2012) The insulin resistance Grb14 adaptor protein promotes thyroid cancer ret signaling and progression. Oncogene 31, 40124021.
  • 35
    Ooi J, Yajnik V, Immanuel D, Gordon M, Moskow JJ, Buchberg AM & Margolis B (1995) The cloning of Grb10 reveals a new family of SH2 domain proteins. Oncogene 10, 16211630.
  • 36
    Laviola L, Giorgino F, Chow JC, Baquero JA, Hansen H, Ooi J, Zhu J, Riedel H & Smith RJ (1997) The adapter protein Grb10 associates preferentially with the insulin receptor as compared with the IGF–I receptor in mouse fibroblasts. J Clin Invest 99, 830837.
  • 37
    Cooney GJ, Lyons RJ, Crew AJ, Jensen TE, Molero JC, Mitchell CJ, Biden TJ, Ormandy CJ, James DE & Daly RJ (2004) Improved glucose homeostasis and enhanced insulin signalling in Grb14-deficient mice. EMBO J 23, 582593.
  • 38
    Kasus-Jacobi A, Perdereau D, Auzan C, Clauser E, Van Obberghen E, Mauvais-Jarvis F, Girard J & Burnol AF (1998) Identification of the rat adapter Grb14 as an inhibitor of insulin actions. J Biol Chem 273, 2602626035.
  • 39
    Smith FM, Holt LJ, Garfield AS, Charalambous M, Koumanov F, Perry M, Bazzani R, Sheardown SA, Hegarty BD, Lyons RJ et al. (2007) Mice with a disruption of the imprinted Grb10 gene exhibit altered body composition, glucose homeostasis, and insulin signaling during postnatal life. Mol Cell Biol 27, 58715886.
  • 40
    Wang L, Balas B, Christ-Roberts CY, Kim RY, Ramos FJ, Kikani CK, Li C, Deng C, Reyna S, Musi N et al. (2007) Peripheral disruption of the Grb10 gene enhances insulin signaling and sensitivity in vivo. Mol Cell Biol 27, 64976505.
  • 41
    Doiron B, Hu W, Norton L & Defronzo RA (2012) Lentivirus shRNA Grb10 targeting the pancreas induces apoptosis and improved glucose tolerance due to decreased plasma glucagon levels. Diabetologia 55, 719728.
  • 42
    Zhang J, Zhang N, Liu M, Li X, Zhou L, Huang W, Xu Z, Liu J, Musi N, Defronzo RA et al. (2012) Disruption of growth factor receptor-binding protein 10 in the pancreas enhances β–cell proliferation and protects mice from streptozotocin-induced β–cell apoptosis. Diabetes 61, 31893198.
  • 43
    Rajala A, Tanito M, Le YZ, Kahn CR & Rajala RV (2008) Loss of neuroprotective survival signal in mice lacking insulin receptor gene in rod photoreceptor cells. J Biol Chem 283, 1978119792.
  • 44
    Nelms K, O'Neill TJ, Li S, Hubbard SR, Gustafson TA & Paul WE (1999) Alternative splicing, gene localization, and binding of SH2–B to the insulin receptor kinase domain. Mamm Genome 10, 11601167.
  • 45
    Osborne MA, Dalton S & Kochan JP (1995) The yeast tribrid system – genetic detection of trans-phosphorylated ITAM–SH2 interactions. Biotechnology 13, 14741478.
  • 46
    Ohtsuka S, Takaki S, Iseki M, Miyoshi K, Nakagata N, Kataoka Y, Yoshida N, Takatsu K & Yoshimura A (2002) SH2–B is required for both male and female reproduction. Mol Cell Biol 22, 30663077.
  • 47
    Riedel H, Wang J, Hansen H & Yousaf N (1997) PSM, an insulin-dependent, pro-rich, PH, SH2 domain containing partner of the insulin receptor. J Biochem 122, 11051113.
  • 48
    Yousaf N, Deng Y, Kang Y & Riedel H (2001) Four PSM/SH2–B alternative splice variants and their differential roles in mitogenesis. J Biol Chem 276, 4094040948.
  • 49
    Yoshiga D, Sato N, Torisu T, Mori H, Yoshida R, Nakamura S, Takaesu G, Kobayashi T & Yoshimura A (2007) Adaptor protein SH2–B linking receptor-tyrosine kinase and Akt promotes adipocyte differentiation by regulating peroxisome proliferator-activated receptor γ messenger ribonucleic acid levels. Mol Endocrinol 21, 11201131.
  • 50
    Duan C, Yang H, White MF & Rui L (2004) Disruption of the SH2–B gene causes age-dependent insulin resistance and glucose intolerance. Mol Cell Biol 24, 74357443.
  • 51
    Kotani K, Wilden P & Pillay TS (1998) SH2–Bα is an insulin-receptor adapter protein and substrate that interacts with the activation loop of the insulin-receptor kinase. Biochem J 335, 103109.
  • 52
    Minami A, Iseki M, Kishi K, Wang M, Ogura M, Furukawa N, Hayashi S, Yamada M, Obata T, Takeshita Y et al. (2003) Increased insulin sensitivity and hypoinsulinemia in APS knockout mice. Diabetes 52, 26572665.
  • 53
    Moodie SA, Alleman-Sposeto J & Gustafson TA (1999) Identification of the APS protein as a novel insulin receptor substrate. J Biol Chem 274, 1118611193.
  • 54
    Li M, Li Z, Morris DL & Rui L (2007) Identification of SH2B2β as an inhibitor for SH2B1- and SH2B2α-promoted Janus kinase–2 activation and insulin signaling. Endocrinology 148, 16151621.
  • 55
    Nantel A, Huber M & Thomas DY (1999) Localization of endogenous Grb10 to the mitochondria and its interaction with the mitochondrial-associated Raf–1 pool. J Biol Chem 274, 3571935724.
  • 56
    Lyons RJ, Deane R, Lynch DK, Ye ZS, Sanderson GM, Eyre HJ, Sutherland GR & Daly RJ (2001) Identification of a novel human tankyrase through its interaction with the adaptor protein Grb14. J Biol Chem 276, 1717217180.
  • 57
    Desbuquois B, Bereziat V, Authier F, Girard J & Burnol AF (2008) Compartmentalization and in vivo insulin-induced translocation of the insulin-signaling inhibitor Grb14 in rat liver. FEBS J 275, 43634377.
  • 58
    Lui JC, Finkielstain GP, Barnes KM & Baron J (2008) An imprinted gene network that controls mammalian somatic growth is down-regulated during postnatal growth deceleration in multiple organs. Am J Physiol Regul Integr Comp Physiol 295, R189R196.
  • 59
    Cao XR, Lill NL, Boase N, Shi PP, Croucher DR, Shan H, Qu J, Sweezer EM, Place T, Kirby PA et al. (2008) Nedd4 controls animal growth by regulating IGF–1 signaling. Sci Signal 1, ra5.
  • 60
    Rampersaud E, Damcott CM, Fu M, Shen H, McArdle P, Shi X, Shelton J, Yin J, Chang YP, Ott SH et al. (2007) Identification of novel candidate genes for type 2 diabetes from a genome-wide association scan in the Old Order Amish: evidence for replication from diabetes-related quantitative traits and from independent populations. Diabetes 56, 30533062.
  • 61
    Di Paola R, Ciociola E, Boonyasrisawat W, Nolan D, Duffy J, Miscio G, Cisternino C, Fini G, Tassi V, Doria A et al. (2006) Association of hGrb10 genetic variations with type 2 diabetes in Caucasian subjects. Diabetes Care 29, 11811183.
  • 62
    Kooner JS, Saleheen D, Sim X, Sehmi J, Zhang W, Frossard P, Been LF, Chia KS, Dimas AS, Hassanali N et al. (2011) Genome-wide association study in individuals of South Asian ancestry identifies six new type 2 diabetes susceptibility loci. Nat Genet 43, 984989.
  • 63
    Manning AK, Hivert MF, Scott RA, Grimsby JL, Bouatia-Naji N, Chen H, Rybin D, Liu CT, Bielak LF, Prokopenko I et al. (2012) A genome-wide approach accounting for body mass index identifies genetic variants influencing fasting glycemic traits and insulin resistance. Nat Genet 44, 659669.
  • 64
    Scott RA, Lagou V, Welch RP, Wheeler E, Montasser ME, Luan J, Magi R, Strawbridge RJ, Rehnberg E, Gustafsson S et al. (2012) Large-scale association analyses identify new loci influencing glycemic traits and provide insight into the underlying biological pathways. Nat Genet 44, 9911005.
  • 65
    Heid IM, Jackson AU, Randall JC, Winkler TW, Qi L, Steinthorsdottir V, Thorleifsson G, Zillikens MC, Speliotes EK, Magi R et al. (2010) Meta-analysis identifies 13 new loci associated with waist–hip ratio and reveals sexual dimorphism in the genetic basis of fat distribution. Nat Genet 42, 949960.
  • 66
    Morris AP, Voight BF, Teslovich TM, Ferreira T, Segre AV, Steinthorsdottir V, Strawbridge RJ, Khan H, Grallert H, Mahajan A et al. (2012) Large-scale association analysis provides insights into the genetic architecture and pathophysiology of type 2 diabetes. Nat Genet 44, 981990.
  • 67
    Bauer F, Elbers CC, Adan RA, Loos RJ, Onland-Moret NC, Grobbee DE, van Vliet-Ostaptchouk JV, Wijmenga C & van der Schouw YT (2009) Obesity genes identified in genome-wide association studies are associated with adiposity measures and potentially with nutrient-specific food preference. Am J Clin Nutr 90, 951959.
  • 68
    Jamshidi Y, Snieder H, Ge D, Spector TD & O'Dell SD (2007) The SH2B gene is associated with serum leptin and body fat in normal female twins. Obesity 15, 59.
  • 69
    Renstrom F, Payne F, Nordstrom A, Brito EC, Rolandsson O, Hallmans G, Barroso I, Nordstrom P & Franks PW (2009) Replication and extension of genome-wide association study results for obesity in 4923 adults from northern Sweden. Hum Mol Genet 18, 14891496.
  • 70
    Thorleifsson G, Walters GB, Gudbjartsson DF, Steinthorsdottir V, Sulem P, Helgadottir A, Styrkarsdottir U, Gretarsdottir S, Thorlacius S, Jonsdottir I et al. (2009) Genome-wide association yields new sequence variants at seven loci that associate with measures of obesity. Nat Genet 41, 1824.
  • 71
    Willer CJ, Speliotes EK, Loos RJ, Li S, Lindgren CM, Heid IM, Berndt SI, Elliott AL, Jackson AU, Lamina C et al. (2009) Six new loci associated with body mass index highlight a neuronal influence on body weight regulation. Nat Genet 41, 2534.
  • 72
    Hotta K, Kitamoto A, Kitamoto T, Mizusawa S, Teranishi H, So R, Matsuo T, Nakata Y, Hyogo H, Ochi H et al. (2012) Association between type 2 diabetes genetic susceptibility loci and visceral and subcutaneous fat area as determined by computed tomography. J Hum Genet 57, 305310.
  • 73
    Bochukova EG, Huang N, Keogh J, Henning E, Purmann C, Blaszczyk K, Saeed S, Hamilton-Shield J, Clayton-Smith J, O'Rahilly S et al. (2010) Large, rare chromosomal deletions associated with severe early-onset obesity. Nature 463, 666670.
  • 74
    Walters RG, Jacquemont S, Valsesia A, de Smith AJ, Martinet D, Andersson J, Falchi M, Chen F, Andrieux J, Lobbens S et al. (2010) A new highly penetrant form of obesity due to deletions on chromosome 16p11.2. Nature 463, 671675.
  • 75
    Cariou B, Capitaine N, Le Marcis V, Vega N, Bereziat V, Kergoat M, Laville M, Girard J, Vidal H & Burnol AF (2004) Increased adipose tissue expression of Grb14 in several models of insulin resistance. FASEB J 18, 965967.
  • 76
    Park JJ, Berggren JR, Hulver MW, Houmard JA & Hoffman EP (2006) GRB14, GPD1, and GDF8 as potential network collaborators in weight loss-induced improvements in insulin action in human skeletal muscle. Physiol Genomics 27, 114121.
  • 77
    Lucas-Fernandez E, Garcia-Palmero I & Villalobo A (2008) Genomic organization and control of the grb7 gene family. Curr Genomics 9, 6068.
  • 78
    Daly RJ, Sanderson GM, Janes PW & Sutherland RL (1996) Cloning and characterization of GRB14, a novel member of the GRB7 gene family. J Biol Chem 271, 1250212510.
  • 79
    Kairouz R, Parmar J, Lyons RJ, Swarbrick A, Musgrove EA & Daly RJ (2005) Hormonal regulation of the Grb14 signal modulator and its role in cell cycle progression of MCF–7 human breast cancer cells. J Cell Physiol 203, 8593.
  • 80
    O-Sullivan I, Chopra A, Carr J, Kim TS & Cohen EP (2008) Immunity to growth factor receptor-bound protein 10, a signal transduction molecule, inhibits the growth of breast cancer in mice. Cancer Res 68, 24632470.
  • 81
    Yu Y, Yoon SO, Poulogiannis G, Yang Q, Ma XM, Villen J, Kubica N, Hoffman GR, Cantley LC, Gygi SP et al. (2011) Phosphoproteomic analysis identifies Grb10 as an mTORC1 substrate that negatively regulates insulin signaling. Science 332, 13221326.
  • 82
    Lin RC, Weeks KL, Gao XM, Williams RB, Bernardo BC, Kiriazis H, Matthews VB, Woodcock EA, Bouwman RD, Mollica JP et al. (2010) PI3K(p110α) protects against myocardial infarction-induced heart failure: identification of PI3K-regulated miRNA and mRNA. Arterioscler Thromb Vasc Biol 30, 724732.
  • 83
    Kato N, Takeuchi F, Tabara Y, Kelly TN, Go MJ, Sim X, Tay WT, Chen CH, Zhang Y, Yamamoto K et al. (2011) Meta-analysis of genome-wide association studies identifies common variants associated with blood pressure variation in east Asians. Nat Genet 43, 531538.
  • 84
    Ungaro P, Teperino R, Mirra P, Longo M, Ciccarelli M, Raciti GA, Nigro C, Miele C, Formisano P & Beguinot F (2010) Hepatocyte nuclear factor (HNF)–4α-driven epigenetic silencing of the human PED gene. Diabetologia 53, 14821492.
  • 85
    Ren D, Zhou Y, Morris D, Li M, Li Z & Rui L (2007) Neuronal SH2B1 is essential for controlling energy and glucose homeostasis. J Clin Invest 117, 397406.
  • 86
    Rea R, Gray S & Donnelly R (2005) Contrasting effects of insulin and cellular differentiation on expression of the novel insulin receptor substrate APS in skeletal muscle. Biochem Pharmacol 70, 13091311.
  • 87
    Kasus-Jacobi A, Bereziat V, Perdereau D, Girard J & Burnol AF (2000) Evidence for an interaction between the insulin receptor and Grb7. A role for two of its binding domains, PIR and SH2. Oncogene 19, 20522059.
  • 88
    Dong LQ, Du H, Porter SG, Kolakowski LF Jr, Lee AV, Mandarino LJ, Fan J, Yee D & Liu F (1997) Cloning, chromosome localization, expression, and characterization of an Src homology 2 and pleckstrin homology domain-containing insulin receptor binding protein hGrb10γ. J Biol Chem 272, 2910429112.
  • 89
    Dong LQ, Porter S, Hu D & Liu F (1998) Inhibition of hGrb10 binding to the insulin receptor by functional domain-mediated oligomerization. J Biol Chem 273, 1772017725.
  • 90
    Hansen H, Svensson U, Zhu J, Laviola L, Giorgino F, Wolf G, Smith RJ & Riedel H (1996) Interaction between the Grb10 SH2 domain and the insulin receptor carboxyl terminus. J Biol Chem 271, 88828886.
  • 91
    He W, Rose DW, Olefsky JM & Gustafson TA (1998) Grb10 interacts differentially with the insulin receptor, insulin-like growth factor I receptor, and epidermal growth factor receptor via the Grb10 Src homology 2 (SH2) domain and a second novel domain located between the pleckstrin homology and SH2 domains. J Biol Chem 273, 68606867.
  • 92
    Liu F & Roth RA (1995) Grb–IR: a SH2-domain-containing protein that binds to the insulin receptor and inhibits its function. Proc Natl Acad Sci USA 92, 1028710291.
  • 93
    O'Neill TJ, Rose DW, Pillay TS, Hotta K, Olefsky JM & Gustafson TA (1996) Interaction of a GRB–IR splice variant (a human GRB10 homolog) with the insulin and insulin-like growth factor I receptors. Evidence for a role in mitogenic signaling. J Biol Chem 271, 2250622513.
  • 94
    Hemming R, Agatep R, Badiani K, Wyant K, Arthur G, Gietz RD & Triggs-Raine B (2001) Human growth factor receptor bound 14 binds the activated insulin receptor and alters the insulin-stimulated tyrosine phosphorylation levels of multiple proteins. Biochem Cell Biol 79, 2132.
  • 95
    Dey BR, Frick K, Lopaczynski W, Nissley SP & Furlanetto RW (1996) Evidence for the direct interaction of the insulin-like growth factor I receptor with IRS–1, Shc, and Grb10. Mol Endocrinol 10, 631641.
  • 96
    Morrione A, Valentinis B, Resnicoff M, Xu S & Baserga R (1997) The role of mGrb10α in insulin-like growth factor I-mediated growth. J Biol Chem 272, 2638226387.
  • 97
    Bereziat V, Kasus-Jacobi A, Perdereau D, Cariou B, Girard J & Burnol AF (2002) Inhibition of insulin receptor catalytic activity by the molecular adapter Grb14. J Biol Chem 277, 48454852.
  • 98
    King CC & Newton AC (2004) The adaptor protein Grb14 regulates the localization of 3–phosphoinositide-dependent kinase–1. J Biol Chem 279, 3751837527.
  • 99
    Rajala A, Daly RJ, Tanito M, Allen DT, Holt LJ, Lobanova ES, Arshavsky VY & Rajala RV (2009) Growth factor receptor-bound protein 14 undergoes light-dependent intracellular translocation in rod photoreceptors: functional role in retinal insulin receptor activation. Biochemistry 48, 55635572.
  • 100
    Monami G, Emiliozzi V & Morrione A (2008) Grb10/Nedd4-mediated multiubiquitination of the insulin-like growth factor receptor regulates receptor internalization. J Cell Physiol 216, 426437.
  • 101
    Goenaga D, Hampe C, Carre N, Cailliau K, Browaeys-Poly E, Perdereau D, Holt LJ, Daly RJ, Girard J, Broutin I et al. (2009) Molecular determinants of Grb14-mediated inhibition of insulin signaling. Mol Endocrinol 23, 10431051.
  • 102
    Stein EG, Gustafson TA & Hubbard SR (2001) The BPS domain of Grb10 inhibits the catalytic activity of the insulin and IGF1 receptors. FEBS Lett 493, 106111.
  • 103
    Langlais P, Dong LQ, Ramos FJ, Hu D, Li Y, Quon MJ & Liu F (2004) Negative regulation of insulin-stimulated mitogen-activated protein kinase signaling by Grb10. Mol Endocrinol 18, 350358.
  • 104
    Wick MJ, Dong LQ, Hu D, Langlais P & Liu F (2001) Insulin receptor-mediated p62dok tyrosine phosphorylation at residues 362 and 398 plays distinct roles for binding GTPase-activating protein and Nck and is essential for inhibiting insulin-stimulated activation of Ras and Akt. J Biol Chem 276, 4284342850.
  • 105
    Wick KR, Werner ED, Langlais P, Ramos FJ, Dong LQ, Shoelson SE & Liu F (2003) Grb10 inhibits insulin-stimulated insulin receptor substrate (IRS)-phosphatidylinositol 3–kinase/Akt signaling pathway by disrupting the association of IRS–1/IRS–2 with the insulin receptor. J Biol Chem 278, 84608467.
  • 106
    Dufresne AM & Smith RJ (2005) The adapter protein GRB10 is an endogenous negative regulator of insulin-like growth factor signaling. Endocrinology 146, 43994409.
  • 107
    Hsu PP, Kang SA, Rameseder J, Zhang Y, Ottina KA, Lim D, Peterson TR, Choi Y, Gray NS, Yaffe MB et al. (2011) The mTOR-regulated phosphoproteome reveals a mechanism of mTORC1-mediated inhibition of growth factor signaling. Science 332, 13171322.
  • 108
    Nouaille S, Blanquart C, Zilberfarb V, Boute N, Perdereau D, Roix J, Burnol AF & Issad T (2006) Interaction with Grb14 results in site-specific regulation of tyrosine phosphorylation of the insulin receptor. EMBO Rep 7, 512518.
  • 109
    Mounier C, Lavoie L, Dumas V, Mohammad-Ali K, Wu J, Nantel A, Bergeron JJ, Thomas DY & Posner BI (2001) Specific inhibition by hGRB10ζ of insulin-induced glycogen synthase activation: evidence for a novel signaling pathway. Mol Cell Endocrinol 173, 1527.
  • 110
    Cariou B, Perdereau D, Cailliau K, Browaeys-Poly E, Bereziat V, Vasseur-Cognet M, Girard J & Burnol AF (2002) The adapter protein ZIP binds Grb14 and regulates its inhibitory action on insulin signaling by recruiting protein kinase Cζ. Mol Cell Biol 22, 69596970.
  • 111
    Langlais P, Wang C, Dong LQ, Carroll CA, Weintraub ST & Liu F (2005) Phosphorylation of Grb10 by mitogen-activated protein kinase: identification of Ser150 and Ser476 of human Grb10ζ as major phosphorylation sites. Biochemistry 44, 88908897.
  • 112
    Carre N, Cauzac M, Girard J & Burnol AF (2008) Dual effect of the adapter growth factor receptor-bound protein 14 (grb14) on insulin action in primary hepatocytes. Endocrinology 149, 31093117.
  • 113
    Deng Y, Zhang M & Riedel H (2008) Mitogenic roles of Gab1 and Grb10 as direct cellular partners in the regulation of MAP kinase signaling. J Cell Biochem 105, 11721182.
  • 114
    Deng Y, Bhattacharya S, Swamy OR, Tandon R, Wang Y, Janda R & Riedel H (2003) Growth factor receptor-binding protein 10 (Grb10) as a partner of phosphatidylinositol 3–kinase in metabolic insulin action. J Biol Chem 278, 3931139322.
  • 115
    Kebache S, Ash J, Annis MG, Hagan J, Huber M, Hassard J, Stewart CL, Whiteway M & Nantel A (2007) Grb10 and active Raf–1 kinase promote Bad-dependent cell survival. J Biol Chem 282, 2187321883.
  • 116
    Nantel A, Mohammad-Ali K, Sherk J, Posner BI & Thomas DY (1998) Interaction of the Grb10 adapter protein with the Raf1 and MEK1 kinases. J Biol Chem 273, 1047510484.
  • 117
    Hu ZQ, Zhang JY, Ji CN, Xie Y, Chen JZ & Mao YM (2010) Grb10 interacts with Bim L and inhibits apoptosis. Mol Biol Rep 37, 35473552.
  • 118
    Shiura H, Miyoshi N, Konishi A, Wakisaka-Saito N, Suzuki R, Muguruma K, Kohda T, Wakana S, Yokoyama M, Ishino F et al. (2005) Meg1/Grb10 overexpression causes postnatal growth retardation and insulin resistance via negative modulation of the IGF1R and IR cascades. Biochem Biophys Res Commun 329, 909916.
  • 119
    Yamamoto Y, Ishino F, Kaneko-Ishino T, Shiura H, Uchio-Yamada K, Matsuda J, Suzuki O & Sato K (2008) Type 2 diabetes mellitus in a non-obese mouse model induced by Meg1/Grb10 overexpression. Exp Anim 57, 385395.
  • 120
    Charalambous M, Smith FM, Bennett WR, Crew TE, Mackenzie F & Ward A (2003) Disruption of the imprinted Grb10 gene leads to disproportionate overgrowth by an Igf2-independent mechanism. Proc Natl Acad Sci USA 100, 82928297.
  • 121
    Charalambous M, Cowley M, Geoghegan F, Smith FM, Radford EJ, Marlow BP, Graham CF, Hurst LD & Ward A (2010) Maternally-inherited Grb10 reduces placental size and efficiency. Dev Biol 337, 18.
  • 122
    Holt LJ, Turner N, Mokbel N, Trefely S, Kanzleiter T, Kaplan W, Ormandy CJ, Daly RJ & Cooney GJ (2012) Grb10 regulates the development of fiber number in skeletal muscle. FASEB J 26, 36583669.
  • 123
    Garfield AS, Cowley M, Smith FM, Moorwood K, Stewart-Cox JE, Gilroy K, Baker S, Xia J, Dalley JW, Hurst LD et al. (2011) Distinct physiological and behavioural functions for parental alleles of imprinted Grb10. Nature 469, 534538.
  • 124
    Asante-Appiah E & Kennedy BP (2003) Protein tyrosine phosphatases: the quest for negative regulators of insulin action. Am J Physiol Endocrinol Metab 284, E663E670.
  • 125
    Holt LJ, Lyons RJ, Ryan AS, Beale SM, Ward A, Cooney GJ & Daly RJ (2009) Dual ablation of Grb10 and Grb14 in mice reveals their combined role in regulation of insulin signaling and glucose homeostasis. Mol Endocrinol 23, 14061414.
  • 126
    Wang J & Riedel H (1998) Insulin-like growth factor–I receptor and insulin receptor association with a Src homology–2 domain-containing putative adapter. J Biol Chem 273, 31363139.
  • 127
    Ahmed Z, Smith BJ, Kotani K, Wilden P & Pillay TS (1999) APS, an adapter protein with a PH and SH2 domain, is a substrate for the insulin receptor kinase. Biochem J 341, 665668.
  • 128
    Ahmed Z & Pillay TS (2003) Adapter protein with a pleckstrin homology (PH) and an Src homology 2 (SH2) domain (APS) and SH2–B enhance insulin-receptor autophosphorylation, extracellular-signal-regulated kinase and phosphoinositide 3-kinase-dependent signalling. Biochem J 371, 405412.
  • 129
    Katsanakis KD & Pillay TS (2005) Cross-talk between the two divergent insulin signaling pathways is revealed by the protein kinase B (Akt)-mediated phosphorylation of adapter protein APS on serine 588. J Biol Chem 280, 3782737832.
  • 130
    Morris DL, Cho KW, Zhou Y & Rui L (2009) SH2B1 enhances insulin sensitivity by both stimulating the insulin receptor and inhibiting tyrosine dephosphorylation of insulin receptor substrate proteins. Diabetes 58, 20392047.
  • 131
    Morris DL, Cho KW & Rui L (2010) Critical role of the Src homology 2 (SH2) domain of neuronal SH2B1 in the regulation of body weight and glucose homeostasis in mice. Endocrinology 151, 36433651.
  • 132
    Zhang M, Deng Y, Tandon R, Bai C & Riedel H (2008) Essential role of PSM/SH2–B variants in insulin receptor catalytic activation and the resulting cellular responses. J Cell Biochem 103, 162181.
  • 133
    Zhang M, Deng Y & Riedel H (2008) PSM/SH2B1 splice variants: critical role in src catalytic activation and the resulting STAT3s-mediated mitogenic response. J Cell Biochem 104, 105118.
  • 134
    Riedel H, Yousaf N, Zhao Y, Dai H, Deng Y & Wang J (2000) PSM, a mediator of PDGF–BB-, IGF–I-, and insulin-stimulated mitogenesis. Oncogene 19, 3950.
  • 135
    Deng Y, Xu H & Riedel H (2007) PSM/SH2–B distributes selected mitogenic receptor signals to distinct components in the PI3-kinase and MAP kinase signaling pathways. J Cell Biochem 100, 557573.
  • 136
    Duan C, Li M & Rui L (2004) SH2–B promotes insulin receptor substrate 1 (IRS1)- and IRS2-mediated activation of the phosphatidylinositol 3–kinase pathway in response to leptin. J Biol Chem 279, 4368443691.
  • 137
    Onnockx S, Xie J, Degraef C, Erneux C & Pirson I (2009) Insulin increase in MAP kinase phosphorylation is shifted to early time-points by overexpressing APS, while Akt phosphorylation is not influenced. Exp Cell Res 315, 24792486.
  • 138
    Liu J, Kimura A, Baumann CA & Saltiel AR (2002) APS facilitates c–Cbl tyrosine phosphorylation and GLUT4 translocation in response to insulin in 3T3–L1 adipocytes. Mol Cell Biol 22, 35993609.
  • 139
    Ahn MY, Katsanakis KD, Bheda F & Pillay TS (2004) Primary and essential role of the adaptor protein APS for recruitment of both c–Cbl and its associated protein CAP in insulin signaling. J Biol Chem 279, 2152621532.
  • 140
    Baumann CA, Ribon V, Kanzaki M, Thurmond DC, Mora S, Shigematsu S, Bickel PE, Pessin JE & Saltiel AR (2000) CAP defines a second signalling pathway required for insulin-stimulated glucose transport. Nature 407, 202207.
  • 141
    Chiang SH, Baumann CA, Kanzaki M, Thurmond DC, Watson RT, Neudauer CL, Macara IG, Pessin JE & Saltiel AR (2001) Insulin-stimulated GLUT4 translocation requires the CAP-dependent activation of TC10. Nature 410, 944948.
  • 142
    Barres R, Gonzalez T, Le Marchand-Brustel Y & Tanti JF (2005) The interaction between the adaptor protein APS and Enigma is involved in actin organisation. Exp Cell Res 308, 334344.
  • 143
    Barres R, Gremeaux T, Gual P, Gonzalez T, Gugenheim J, Tran A, Le Marchand-Brustel Y & Tanti JF (2006) Enigma interacts with adaptor protein with PH and SH2 domains to control insulin-induced actin cytoskeleton remodeling and glucose transporter 4 translocation. Mol Endocrinol 20, 28642875.
  • 144
    Li M, Ren D, Iseki M, Takaki S & Rui L (2006) Differential role of SH2–B and APS in regulating energy and glucose homeostasis. Endocrinology 147, 21632170.
  • 145
    Ren D, Li M, Duan C & Rui L (2005) Identification of SH2–B as a key regulator of leptin sensitivity, energy balance, and body weight in mice. Cell Metab 2, 95104.
  • 146
    Barbieri M, Bonafe M, Franceschi C & Paolisso G (2003) Insulin/IGF–I-signaling pathway: an evolutionarily conserved mechanism of longevity from yeast to humans. Am J Physiol Endocrinol Metab 285, E1064E1071.
  • 147
    Giannakou ME & Partridge L (2007) Role of insulin-like signalling in Drosophila lifespan. Trends Biochem Sci 32, 180188.
  • 148
    Werz C, Kohler K, Hafen E & Stocker H (2009) The Drosophila SH2B family adaptor Lnk acts in parallel to Chico in the insulin signaling pathway. PLoS Genet 5, e1000596.
  • 149
    Slack C, Werz C, Wieser D, Alic N, Foley A, Stocker H, Withers DJ, Thornton JM, Hafen E & Partridge L (2010) Regulation of lifespan, metabolism, and stress responses by the Drosophila SH2B protein, Lnk. PLoS Genet 6, e1000881.
  • 150
    Song W, Ren D, Li W, Jiang L, Cho KW, Huang P, Fan C, Song Y, Liu Y & Rui L (2010) SH2B regulation of growth, metabolism, and longevity in both insects and mammals. Cell Metab 11, 427437.
  • 151
    Morrione A, Plant P, Valentinis B, Staub O, Kumar S, Rotin D & Baserga R (1999) mGrb10 interacts with Nedd4. J Biol Chem 274, 2409424099.
  • 152
    Vecchione A, Marchese A, Henry P, Rotin D & Morrione A (2003) The Grb10/Nedd4 complex regulates ligand-induced ubiquitination and stability of the insulin-like growth factor I receptor. Mol Cell Biol 23, 33633372.
  • 153
    Huang Q & Szebenyi DM (2010) Structural basis for the interaction between the growth factor-binding protein GRB10 and the E3 ubiquitin ligase NEDD4. J Biol Chem 285, 4213042139.
  • 154
    Ramos FJ, Langlais PR, Hu D, Dong LQ & Liu F (2006) Grb10 mediates insulin-stimulated degradation of the insulin receptor: a mechanism of negative regulation. Am J Physiol Endocrinol Metab 290, E1262E1266.
  • 155
    Ahmed Z, Smith BJ & Pillay TS (2000) The APS adapter protein couples the insulin receptor to the phosphorylation of c–Cbl and facilitates ligand-stimulated ubiquitination of the insulin receptor. FEBS Lett 475, 3134.
  • 156
    Wilcox A, Katsanakis KD, Bheda F & Pillay TS (2004) Asb6, an adipocyte-specific ankyrin and SOCS box protein, interacts with APS to enable recruitment of elongins B and C to the insulin receptor signaling complex. J Biol Chem 279, 3888138888.
  • 157
    Kishi K, Mawatari K, Sakai-Wakamatsu K, Yuasa T, Wang M, Ogura-Sawa M, Nakaya Y, Hatakeyama S & Ebina Y (2007) APS-mediated ubiquitination of the insulin receptor enhances its internalization, but does not induce its degradation. Endocr J 54, 7788.