Protein Phosphorylation and Insulin Action

  • N. Perrotti
  • D. Accili
  • S. A. Phillips
  • S. I. Taylor
Part of the Advances in Experimental Medicine and Biology book series (NATO ASI F, volume 231)


Protein phosphorylation is an important mechanism of regulation in many metabolic pathways.In muscle glycogen metabolism,the enzymes involved in anabolic steps are activated by a dephosphorylation,the enzymes involved in catabolic steps are activated by a phosphorylation.


Insulin Receptor Tyrosine Phosphorylation Insulin Action Tyrosine Kinase Activity Insulin Binding 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Foulkes J.G., Jefferson L.S.,Cohen P. (1980).The hormonal control of glycogen metabolism:dephosphorylation of protein phosphatase inhibitor-1 in vivo in response to insulin. FEBS LETTERS 112–21.Google Scholar
  2. 2.
    Seals J.R., McDonald J.M., Jarrett L. (1979). Insulin effect on protein phosphorylation of plasma membranes and mitochondria in a subcellular system from rat adipocytes. The Journal of Biological Chemistry. 254–6997.Google Scholar
  3. 3.
    Cohen P. (1982). The role of protein phosphorylation in neural and hormonal control of cellular activity. Nature 296–613.Google Scholar
  4. 4.
    Kasuga M.,Karlsson F.A.,Kahn C.R. (1982).Insulin stimulates the phosphorylation of the 95,000 Dalton subunit of its own receptor. Science 215–185.Google Scholar
  5. 5.
    Perrotti N., Taylor S.I., Richert N.D., Rapp U.R., Pastan I.H., Roth J. (1985).Immunoprecipitation of insulin receptors from cultured human lymphoblats (IM-9 cells) by antibodies to pp60src. Science 226–761.Google Scholar
  6. 6.
    Ullrich A., Bell G.R.,Chen E.Y.,Herrera R.,Petruzzelli L.M.,Dull T.J.,Gray A.,Coussens L.,Liao Y.C.,Tsubokawa M.,Mason A.,Seeburg P.H., Grunfeld C.,Rosen O.M.,Ramachandran J. (1985).Human insulin receptor and its relationship to the tyrosine kinase family of oncogenes. Nature 313–756.Google Scholar
  7. 7.
    Downward J., Yarden Y., Mayes E., Scrace G.,Totty N., Stockwell P., Ullrich A., Schlessinger J., Waterfield M.D. (1984) Close similarity of epidermal growth factor receptor and v-Erb B oncogene protein sequences. Nature 307–521.Google Scholar
  8. 8.
    Simpson I.A., Hedo J.A. (1984). Insulin receptor phosphorylation may not be a prerequisite for acute insulin action. Science 223–1301.Google Scholar
  9. 9.
    Ellis E.,Clauser E.,Morgan D.O.,Edery M.,Roth R.A.,Rutter W.J. (1986). Replacement of insulin receptors tyrosine residues 1162 and 1163 compromises insulin-stimulated kinase activity and uptake of 2-deoxyglucose. Cell 45–721.Google Scholar
  10. 10.
    Morgan D.O.,Ho L.,Korn L.J.,Roth R.A. (1986). Insulin action is blocked by a monoclonal antibody that inhibits the insulin receptor kinase. Proceedings of the National Academy of Science U.S.A. 83–328.Google Scholar
  11. 11.
    Grunberger G., Comi R.J., Taylor S.I., Gorden P. (1984). Tyrosine kinase activity of the insulin receptor of patients with type A Extreme insulin resistance:Sudies with circulating mononuclear cells and cultured lymphocytes. Journal of Clinical Endocrinology and Metabolism. 59–1152.Google Scholar
  12. 12.
    Grnberger G.,Zick Y.,Gorden P. (1984). Defect in phosphorylation of insulin receptors in cells from an insulin-resistant patient with normal insulin binding. Science 223–932.Google Scholar
  13. 13.
    Caro J.F.,Ittoop 0.,Pories W.J.,Meelheim D.,Flickinger E.G.,Thomas F.,Jenquin M.,Silverman J.F.,Khazanie P.G.,Sinha M.K. (1986). Studies on the mechanism of insulin resistance in liver from humans with non insulin dependent diabetes. Journal of Clinical Investigations.78–249.Google Scholar
  14. 14.
    Comi R.J.,Grunberger G.,Gorden P. (1987) Relationship of insulin binding and insulin-stimulated tyrosine kinase activity is altered in type 2 diabetes. Journal of Clinical Investigations 79–453.Google Scholar
  15. 15.
    Kohno M.(1985). Diverse mitogenic agents induce rapid phosphorylation of a common set of cellular proteins at tyrosine in quiescent mammalian cells.The Journal of Biological Chemistry.260–1771.Google Scholar
  16. 16.
    Cooper J.A.,Hunter T. (1983).Identification and characterization of cellular targets for tyrosine protein kinases.The Journal of Biological Chemistry.258–1108.Google Scholar
  17. 17.
    Cheng Y.S.E., Chen L.B. (1981) Detection of phosphotyrosine-containing 34,000-dalton protein in the framework of cells transformed with Rous sarcoma virus. Proceedings of the National Academy of Science U.S.A. 78–2388.Google Scholar
  18. 18.
    Rees-Jones R.W.,Taylor S.I. (1985).An endogenous substrate for the insulin receptor associated tyrosine kinase.Journal of Biological Chemistry 260–4461.Google Scholar
  19. 19.
    Accili D.,Perrotti N.,Rees-Jones R.W.,Taylor S.I. (1986).Tissue distribution and subcellular localization of an endogenous substrate (pp-120) for the insulin receptor-associated tyrosine kinase. Endocrinology 119–1274.Google Scholar
  20. 20.
    Kamps M.P.,Buss J.E.,Sefton B.M. (1986). Rous sarcoma virus transforming protein lacking myristic acid phosphorylates known polypeptide substrates without inducing transformation. Cell 45–105.Google Scholar
  21. 21.
    Hedo J.A.,Collier E.,Watkinson A. (1987) Myristyl and palmityl acylation of the insulin receptor.Journal of Biological Chemistry.262–2436.Google Scholar
  22. 22.
    Phillips S.A.,Perrotti N.,Taylor S.I. (1987).Rat liver membranes contain a 120 KDa glycoprotein which serves as a substrate for the tyrosine kinases of the receptors for insulin and epidermal growth factor. FEBS Letters.212–141.Google Scholar
  23. 23.
    White M.F.,Maron R.Kahn C.R.(1985). Insulin rapidly stimulates tyrosine phosphorylation of a Mr-185,000 protein in intact cells.Nature 318–183.Google Scholar
  24. 24.
    Häring H.U., White M.F., Machicao F., Ermel B., Schleicher E., Obermaier B. (1987).Insulin rapidly stimulates phosphorylation of a 46-KDa membrane protein on tyrosine residues as well as phosphorylation of several soluble proteins in intact fat cells. Proceedings of the National Academy of Science.U.S.A.84–113.Google Scholar
  25. 25.
    Smith R.J., Beguinot F., White M.F., Maron R., Moses A.C., Wang P.H., Kahn C.R. (1986).The insulin receptor phosphorylates the type 1 insulin like growth factor receptor in intact skeletal muscle cells.III International Symposium on insulin receptors and insulin action.Madrid.Google Scholar
  26. 26.
    Perrotti N., Accili D., Samuels B.M., Rees Jones R.W., Taylor S.I. Insulin stimulates phosphorylation of a 120 KDa glycoprotein substrate (pp-120) for the receptor associated protein kinase in inatact H-35 hepatoma cells. Proceedings of the National Academy of Science. U.S.A. 1987.84–3137.Google Scholar

Copyright information

© Springer Science+Business Media New York 1988

Authors and Affiliations

  • N. Perrotti
    • 1
  • D. Accili
    • 2
  • S. A. Phillips
    • 2
  • S. I. Taylor
    • 2
  1. 1.Clinica Medica IIUniversity of NaplesItaly
  2. 2.Diabetes BranchN.I.H.BethesdaUSA

Personalised recommendations