Skip to main content
SpringerLink
Log in

Binding of SH2 containing proteins to the insulin receptor: A new way for modulating insulin signalling

  • Chapter
Insulin Action

Part of the book series: Developments in Molecular and Cellular Biochemistry ((DMCB,volume 24))

Abstract

Prior studies have established a role in insulin action for the tyrosine phosphorylation of substrates and their subsequent complexing with SH2 containing proteins. More recently, SH2 proteins have been identified which can tightly bind to the tyrosine phosphorylated insulin receptor. The major protein identified so far (called Grb-IR or Grbl0) of this type appears to be present in at least 3 isoforms, varying in the presence of a pleckstrin homology domain and in the sequence of its amino terminus. The binding of this protein to the insulin receptor appears to inhibit signalling by the receptor. The present review will discuss the current knowledge of the structure and function of this protein. (Mol Cell Biochem 182: 73-78, 1998)

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 129.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 169.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

Abbreviations

CHO:

Chinese hamster ovary

EGF:

epidermal growth factor

GST:

glutathione S-transferase

IGF:

l—insulin-like growth factor-1

IR:

insulin receptor

IR-1:

insulin receptor substrate 1

MAP:

mitogen-activated protein

PAGE:

polyacrylamide gel electrophoresis

PDGF:

platelet-derived growth factor receptor

PH:

pleckstrin homology

PI-3-kinase:

phosphatidylinositol 3-kinase

PMSF:

phenylmethanesulphonyl fluoride

SH2:

Src homology 2

References

  1. White MF, Kahn CR: The insulin signalling system. J Biol Chem 269(1): 1–4, 1994

    PubMed  CAS  Google Scholar 

  2. Cheatham B, Kahn CR: Insulin action and the insulin signalling network. Endocrine Rev 16: 117–142, 1995

    CAS  Google Scholar 

  3. Kotani K, Yonezawa K, Hara K, Ueda H, Kitamura Y, Sakaue H, Ando A, Chavanieu B, Calas B, Grigorescu F, Nishiyama M, Waterfield M, Kasuga M: Involvement of phosphoinositide 3-kinase in insulin-or IGF-I-induced membrane ruffling. EMBOJ 13: 2313–2321, 1994

    CAS  Google Scholar 

  4. Burgering BMT, Coffer PJ: Protein kinase B (c-Akt) in phosphatidyl-inositol-3OH kinase signal transduction. Nature 376: 599–602, 1995

    Article  PubMed  CAS  Google Scholar 

  5. Franke TF, Yang SI, Chan TO, Kazlauskas A, Morrison DK, Kaplan DR, Tsichlis PN: The protein kinase encoded by the Akt proto-oncogene is a target of the PDGF-activated phosphatidylinositol 3-kinase. Cell 81: 727–736, 1995

    Article  PubMed  CAS  Google Scholar 

  6. Kohn AD, Kovacina KS, Roth RA: Insulin stimulates the kinase activity of RACPK, a pleckstrin homology domain containing ser/thr kinase. EMBOJ 14: 4288–4295, 1995

    CAS  Google Scholar 

  7. Kaliman P, Vinals F, Testar X, Palacin M, Zorzano A: Phosphatidylinositol 3-kinase inhibitors block differentiation of skeletal muscle cells. J Biol Chem 271: 19146–19151, 1996

    Article  PubMed  CAS  Google Scholar 

  8. Evans J, Honer C, Womelsdorf B, Kaplan E, Bell P: The effects of wortmannin, a potent inhibitor of phosphatidylinositol 3-kinase, on insulin-stimulated glucose transport, GLUT4 translocation, antilipolysis, and DNA synthesis. Cell Sig 7: 365–376, 1995

    Article  CAS  Google Scholar 

  9. Hara K, Yonezawa K, Sakaue H, Ando A, Kotani K, Kitamura Y, Ueda H, Stephens L, Jackson T, Hawkins P, Dhand R, Clark A, Holman G, Waterfield M, Kasuga M: 1-Phosphatidylinositol 3-kinase activity is required for insulin-stimulated glucose transport but not for RAS activation in CHO cells. Proc Natl Acad Sci USA (91): 7415–7419, 1994

    Article  PubMed  CAS  Google Scholar 

  10. Martin S, Haruta T, Morris A, Klippel A, Williams L, Olefsky J: Activated phosphatidylinositol 3-kinase is sufficient to mediate acting rearrangement and GLUT4 translocation in 3T3-L1 adipocytes. J Biol Chem271: 17605-17608, 1996

    Google Scholar 

  11. Skolnik EY, Lee C-H, Batzer A, Vicentini LM, Zhou M, Daly R, Myers MJ Jr, Backer JM, Ullrich A, White MF, Schlessinger J: The SH2/SH3 domain-containing protein GRB2 interacts with tyrosine-phosphorylated 1RS 1 and Shc: Implications for insulin control of ras signalling. EMBOJ 12(5): 1929–1936, 1993

    CAS  Google Scholar 

  12. Skolnik E, Batzer A, Li N, Lee C, Lowenstein E, Mohammadi M, Margolis B, Schlessinger J: The function of GRB2 in linking the insulin receptor to Ras signalling pathways. Science 260: 1953–1955, 1993

    Article  PubMed  CAS  Google Scholar 

  13. Yonezawa K, Ando A, Kaburagi Y, R. Y-H, Kitamura T, Hara K, Nakafuku M, Okabayashi Y, Kadowaki T, Kaziro Y, Kasuga M: Signal transduction pathways from insulin receptors to Ras. Analysis by mutant insulin receptors. J Biol Chem 269(6): 4634–4640, 1994

    PubMed  CAS  Google Scholar 

  14. Kovacina KS, Roth RA: Identification of SHC as a substrate of the insulin receptor kinase distinct from the GAP-associated 62 kDa tyrosine phosphoprotein. Biochem Biophys Res Comm 192: 1303–1311, 1993

    Article  PubMed  CAS  Google Scholar 

  15. Chang P, Le Marchand-Brustel Y, Cheathan L, Moller D: Insulin stimulation of mitogen-activated protein kinase, p90rsk, and p70 S6 kinase in skeletal muscle of normal and insulin-resistant n-iice. Implications for the regulation of glycogen synthase. J Biol Chem 270: 29928–29935, 1995

    Article  PubMed  CAS  Google Scholar 

  16. Denton R, Tavare J: Does mitogen-activated-protein kinase have a role in insulin action? The cases for and against. Eur J Biochem 227: 597–611, 1995

    Article  PubMed  CAS  Google Scholar 

  17. Sale E, Atkinson P, Sale G: Requirement of MAP kinase for differentiation of fibroblasts to adipocytes, for insulin activation of p90 S6 kinase and for insulin or serum stimulation of DNA synthesis. EMBO J 14: 674–684, 1995

    PubMed  CAS  Google Scholar 

  18. Zhang B, Berger J, Zhou G, Elbrecht A, Biswas S, White-Carrington S, Szalkowski D, Moller D: Insulin-and mitogen-activated protein kinase-mediated phosphorylation and activation of peroxisome proliferator-activated receptorγ. J Biol Chem 271: 31771–31774, 1996

    Article  PubMed  CAS  Google Scholar 

  19. Patti M, Sun X, Bruening J, Araki E, Lipes M, White M, Kahn C: 4PS/ insulin receptor substrate (IRS)-2 is the alternative substrate of the insulin receptor in IRS-1-deficient mice. J Biol Chem 270: 24670–24673, 1995

    Article  PubMed  CAS  Google Scholar 

  20. Sun X-J, Wang L-M, Zhang Y, Yenush L, Myers M, Glasheen E, Lane W, Pierce J, White M: Role of IRS-2 in insulin and cytokine signalling. Nature 377: 173–177, 1995

    Article  PubMed  CAS  Google Scholar 

  21. Tobe K, Tamemoto H, Yamauchi T, Aizawa S, Yazaki Y, Kadowaki T: Identification of a 190 kDa protein as a novel substrate for the insulin receptor kinase functionally similar to insulin receptor substrate-1. J Biol Chem 270: 5698–5701, 1995

    Article  PubMed  CAS  Google Scholar 

  22. Myers MJ, Sun XJ, White MF: The IRS-1 signalling system. Trends Biochem Sci 19(7): 289–293, 1994

    Article  PubMed  CAS  Google Scholar 

  23. Liu F, Roth RA: Grb-IR: A SH2-domain-containing protein that binds to and inhibits insulin receptor function. Proc Natl Acad Sci USA 92: 1995

    Google Scholar 

  24. Margolis B, Silvennoinen O, Comoglio F, Roonprapunt C, Skolnik E, Ullrich A, Schlessinger J: High-efficiency expression/cloning of epidermal growth factor-receptor-binding proteins with Src homology 2 domains. Proc Natl Acad Sci USA 89: 8894–8898, 1992

    Article  PubMed  CAS  Google Scholar 

  25. Ooi J, Yajnik V, Immanuel D, Gordon M, Moskow JJ, Buchberg AM, Margolis B: The cloning of Grbl0 reveals a new family of SH2 domain proteins. Oncogene 10: 1610–1630, 1995

    Google Scholar 

  26. Daly R, Sanderson G, Janes P, Sutherland R: Cloning and characterization of Grb14, a novel member of the Grb7 gene family. J Biol Chem 271: 12502–12510, 1996

    Article  PubMed  CAS  Google Scholar 

  27. Gagel R: Putting the bits and pieces of the RET proto-oncogene puzzle together. Bone 17: 13S–16S, 1995

    Article  PubMed  CAS  Google Scholar 

  28. Takahashi S, Uchida K, Nakagawa A, Miyake Y, Kainosho M, Matsuzaki K, Omura S: Biosynthesis of lactacystin. Jour Antibio 48: 1015–1020, 1995

    Article  CAS  Google Scholar 

  29. O’Neill T, Rose T, Pillay T, Hotta K, Olefsky J, Gustafson T: Interaction of a GRB-IR splice variant (a human GRB10 homolog) with the insulin and insulin-like growth factor 1 receptors. Evidence for a role in mitogenic signalling. J Biol Chem 271: 22506–22513, 1996

    Article  PubMed  Google Scholar 

  30. Frantz J, Giorgetti-Peraldi S, Ottinger E, Shoelson S: Human GRB-IRbeta/ GRB 10. Splice variants of an insulin and growth factor receptor-binding protein with PH and SH2 domains. J Biol Chem 272: 2659–2667, 1997

    Article  PubMed  CAS  Google Scholar 

  31. Margolis B: The GRB family of SH2 domain proteins. Prog Biophys Mol Biol 62: 223–244, 1994

    Article  PubMed  CAS  Google Scholar 

  32. Choi KY, Satterberg B, Lyons DM, Elion EA: Ste5 tethers multiple protein kinases in the MAP kinase cascade required for mating in S. cerevisiae.. Cell 78: 499–512, 1994

    CAS  Google Scholar 

  33. Marcus S, Polverino A, Barr M, Wigler M: Complexes between STE5 and components of the pheromone-responsive mitogen-activated protein kinase module. Proc Natl Acad Sci USA 91: 7762–7766, 1994

    Article  PubMed  CAS  Google Scholar 

  34. Klauck T, Faux M, Labudda K, Langeberg L, Jaken S, Scott J: Coordination of three signalling enzymes by AKAP79, a mammalian scaffold protein. Science 271: 1589–1592, 1996

    Article  PubMed  CAS  Google Scholar 

  35. Faux M, Scott J: Molecular glue: Kinase anchoring and scaffold proteins. Cell 85: 9–12, 1996

    Article  PubMed  CAS  Google Scholar 

  36. Yokote K, Margolis B, Heldin C-H, Claesson-Welsh L: Grb7 is a downstream signalling component of platelet-derived growth factor a-and β-receptors. J Biol Chem 271: 30942–30949, 1996

    Article  PubMed  CAS  Google Scholar 

  37. Stein D, Wu J, Fuqua SAW, Roonprapunt C, Yajnik V, d’Eustachio P, Moskow JJ, Buchberg AM, Osborne CK, Margolis B: The SH2 domain protein GRB-7 is co-amplified, overexpressed and in a tight complex with HER2 in breast cancer. EMBOJ 13: 1331–1340, 1994

    CAS  Google Scholar 

  38. Hansen H, Svensson U, Zhu J, Laviola L, Giorgino F, Wolf G, Smith R, Riedel H: Interaction between the Grbl0 SH2 domain and the insulin receptor carboxyl terminus. J Biol Chem 271: 8882–8886. 1996

    Article  PubMed  CAS  Google Scholar 

  39. Pandey A, Liu X, Dixon J, Di Fiore P, Dixit V: Direct association between the Ret receptor tyrosine kinase and the Src homology 2-containing adaptor protein Grb7. J Biol Chem 271: 10607–10610, 1996

    Article  PubMed  CAS  Google Scholar 

  40. Dey BR, Frick K, Lopaczynski W, Nissley SP, Furlanetto RW: Evidence for the direct interaction of the insulin-like growth factor 1 receptor with IRS-1, Shc, and Grbl0. Mol Endocrin 10: 631–641, 1996

    Article  CAS  Google Scholar 

  41. Morrione A, Valentinis B, Li S, Ooi J, Margolis B, Baserga R: Grb10: A new substrate of the insulin-like growth factor I receptor. Cancer Res 56: 3165–3167, 1996

    PubMed  CAS  Google Scholar 

  42. Stein E, Cerretti D, Daniel T: Ligand activation of ELK receptor tyrosine kinase promotes its association with GrblO and Grb2 in vascular endothelial cells. J Biol Chem 271: 23588–23593, 1996

    Article  PubMed  CAS  Google Scholar 

  43. Pandey A, Duan H, Di Fiore P, Dixit V: The Ret receptor protein tyrosine kinase associates with the SH2-containing adaptor protein Grbl0. J Biol Chem 270: 21461–21463, 1995

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Pharmacology, University of Texas Health Science Center at San Antonio, San Antonio, Texas

    Feng Liu

  2. Department of Molecular Pharmacology, Stanford University School of Medicine, Stanford, CA, USA

    Richard A. Roth

Authors
  1. Feng Liu
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Richard A. Roth
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Centre Hospitalier de l’Université de Montreal Pavillion Hotel Dieu, 3840, Rue Saint-Urbain, Montreal, Quebec, H2W 1T8, Canada

    Ashok K. Srivastava

  2. Polypeptide Hormone Laboratory Strathcona Anatomy & Dentistry Building, 3640 University Street, Room W3, 15, Montreal, Quebec, H3A 2B2, Canada

    Barry I. Posner

Rights and permissions

Reprints and permissions

Copyright information

© 1998 Springer Science+Business Media Dordrecht

About this chapter

Cite this chapter

Liu, F., Roth, R.A. (1998). Binding of SH2 containing proteins to the insulin receptor: A new way for modulating insulin signalling. In: Srivastava, A.K., Posner, B.I. (eds) Insulin Action. Developments in Molecular and Cellular Biochemistry, vol 24. Springer, Boston, MA. https://doi.org/10.1007/978-1-4615-5647-3_8

Download citation

  • DOI: https://doi.org/10.1007/978-1-4615-5647-3_8

  • Publisher Name: Springer, Boston, MA

  • Print ISBN: 978-1-4613-7584-5

  • Online ISBN: 978-1-4615-5647-3

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics

Search

Navigation