Historical Background
The Src Homology 2 (SH2) domain-containing adaptor proteins are a class of signal transducers downstream of growth factor receptors. The human genome encodes more than one hundred SH2 domain-containing proteins. The GRB7 family of SH2 domain-containing adaptor proteins includes three members: GRB7, GRB10, and GRB14. All three family members have the same domain structure (Fig. 1). Human GRB10 was originally identified in a yeast-two hybrid screen using the insulin receptor (IR) as bait and named as GRB-IR (Liu and Roth 1995).
GRB7 family proteins share similar domains.GRB7 family proteins share a similar domain arrangement. An N-terminal still un-characterized region followed by a RAS-associated like (RA) domain, which is known to bind with RAS superfamily proteins. The pleckstrin homology (PH) domain binds to phospholipids and recruits proteins to the cell membrane. The Src Homology 2 (SH2) domain is a...
This is a preview of subscription content, log in via an institution.
Buying options
Tax calculation will be finalised at checkout
Purchases are for personal use only
Learn about institutional subscriptionsReferences
Deng Y, Bhattacharya S, Swamy OR, Tandon R, Wang Y, Janda R, et al. Growth factor receptor-binding protein 10 (Grb10) as a partner of phosphatidylinositol 3-kinase in metabolic insulin action. J Biol Chem. 2003;278:39311–22. https://doi.org/10.1074/jbc.M304599200.
Deng Y, Zhang M, Riedel H. Mitogenic roles of Gab1 and Grb10 as direct cellular partners in the regulation of MAP kinase signaling. J Cell Biochem. 2008;105:1172–82. https://doi.org/10.1002/jcb.21829.
Dong LQ, Du H, Porter SG, Kolakowski Jr LF, Lee AV, Mandarino LJ, et al. Cloning, chromosome localization, expression, and characterization of an Src homology 2 and pleckstrin homology domain-containing insulin receptor binding protein hGrb10gamma. J Biol Chem. 1997;272:29104–12.
Frantz JD, Giorgetti-Peraldi S, Ottinger EA, Shoelson SE. Human GRB-IRbeta/GRB10. Splice variants of an insulin and growth factor receptor-binding protein with PH and SH2 domains. J Biol Chem. 1997;272:2659–67.
Hansen H, Svensson U, Zhu J, Laviola L, Giorgino F, Wolf G, et al. Interaction between the Grb10 SH2 domain and the insulin receptor carboxyl terminus. J Biol Chem. 1996;271:8882–6.
He W, Rose DW, Olefsky JM, Gustafson TA. 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. 1998;273:6860–7.
Hsu PP, Kang SA, Rameseder J, Zhang Y, Ottina KA, Lim D, et al. The mTOR-regulated phosphoproteome reveals a mechanism of mTORC1-mediated inhibition of growth factor signaling. Science. 2011;332:1317–22. https://doi.org/10.1126/science.1199498.
Jahn T, Seipel P, Urschel S, Peschel C, Duyster J. Role for the adaptor protein Grb10 in the activation of Akt. Mol Cell Biol. 2002;22:979–91.
Kabir NN, Kazi JU. Grb10 is a dual regulator of receptor tyrosine kinase signaling. Mol Biol Rep. 2014;41:1985–92. https://doi.org/10.1007/s11033-014-3046-4.
Kazi JU, Rönnstrand L. FLT3 signals via the adapter protein Grb10 and overexpression of Grb10 leads to aberrant cell proliferation in acute myeloid leukemia. Mol Oncol. 2013;7:402–18. https://doi.org/10.1016/j.molonc.2012.11.003.
Langlais P, Dong LQ, Hu D, Liu F. Identification of Grb10 as a direct substrate for members of the Src tyrosine kinase family. Oncogene. 2000;19:2895–903. https://doi.org/10.1038/sj.onc.1203616.
Laviola L, Giorgino F, Chow JC, Baquero JA, Hansen H, Ooi J, et al. The adapter protein Grb10 associates preferentially with the insulin receptor as compared with the IGF-I receptor in mouse fibroblasts. J Clin Invest. 1997;99:830–7. https://doi.org/10.1172/JCI119246.
Liu F, Roth RA. Grb-IR: a SH2-domain-containing protein that binds to the insulin receptor and inhibits its function. Proc Natl Acad Sci USA. 1995;92:10287–91.
Morrione A, Plant P, Valentinis B, Staub O, Kumar S, Rotin D, et al. mGrb10 interacts with Nedd4. J Biol Chem. 1999;274:24094–9.
Ramos FJ, Langlais PR, Hu D, Dong LQ, Liu F. Grb10 mediates insulin-stimulated degradation of the insulin receptor: a mechanism of negative regulation. Am J Physiol Endocrinol Metab. 2006;290:E1262–6. https://doi.org/10.1152/ajpendo.00609.2005.
Stein EG, Gustafson TA, Hubbard SR. The BPS domain of Grb10 inhibits the catalytic activity of the insulin and IGF1 receptors. FEBS Lett. 2001;493:106–11.
Vecchione A, Marchese A, Henry P, Rotin D, Morrione A. The Grb10/Nedd4 complex regulates ligand-induced ubiquitination and stability of the insulin-like growth factor I receptor. Mol Cell Biol. 2003;23:3363–72.
Wang J, Dai H, Yousaf N, Moussaif M, Deng Y, Boufelliga A, et al. Grb10, a positive, stimulatory signaling adapter in platelet-derived growth factor BB-, insulin-like growth factor I-, and insulin-mediated mitogenesis. Mol Cell Biol. 1999;19:6217–28.
Wick KR, Werner ED, Langlais P, Ramos FJ, Dong LQ, Shoelson SE, et al. 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. 2003;278:8460–7. https://doi.org/10.1074/jbc.M208518200.
Yu Y, Yoon SO, Poulogiannis G, Yang Q, Ma XM, Villen J, et al. Phosphoproteomic analysis identifies Grb10 as an mTORC1 substrate that negatively regulates insulin signaling. Science. 2011;332:1322–6. https://doi.org/10.1126/science.1199484.
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2018 Springer International Publishing AG
About this entry
Cite this entry
Kabir, N.N., Rönnstrand, L., Kazi, J.U. (2018). GRB10. In: Choi, S. (eds) Encyclopedia of Signaling Molecules. Springer, Cham. https://doi.org/10.1007/978-3-319-67199-4_101665
Download citation
DOI: https://doi.org/10.1007/978-3-319-67199-4_101665
Published:
Publisher Name: Springer, Cham
Print ISBN: 978-3-319-67198-7
Online ISBN: 978-3-319-67199-4
eBook Packages: Biomedical and Life SciencesReference Module Biomedical and Life Sciences