Abstract
Abundant evidence indicates that protein phosphorylation and dephosphorylation of tyrosine, serine, and threonine residues are key mechanisms by which insulin regulates cell function (for review see Ref. 1). The βsubunit of the insulin receptor is a tyrosine kinase activated by insulin binding that catalyzes autophosphorylation and phosphorylation of other proteins (2,3). The intrinsic tyrosine kinase activity of the insulin receptor appears to be critical for insulin action since cells transfected with kinase-deficient mutant insulin receptors (4) or cells injected with antibodies that inhibit the receptor kinase (5) become insensitive to insulin. A current working hypothesis is that activation of the insulin receptor kinase catalyzes the phosphorylation of tyrosine residues on several proteins. These proteins, in turn, regulate the more abundant serine kinases that phosphorylate proteins involved in the end-response.
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References
O.M. Rosen, After insulin binds, Science 237:1452 (1987)
M. Kasuga, Y. Zick, D.L. Blithe, M. Crettaz, and C.R. Kahn, Insulin stimulates tyrosine phosphorylation of the insulin receptor in a cell-free system, Nature 298:667 (1982)
M.F. White, R. Maron, and C.R. Kahn, Insulin rapidly stimulates tyrosine phosphorylation of a Mr 185,000 protein in intact cells, Nature318:183 (1985)
D.A. McClain, H. Maegawa, J. Lee, T.J. Dull, A. Ullrich, and J.M. Olefsky, A mutant insulin receptor with defective tyrosine kinase displays no biological activity and does not undergo endocytosis. J. Biol. Chem. 262:14663 (1987)
D.O. Morgan and R.A. Roth, Acute insulin action requires insulin receptor kinase activity: Introduction of an inhibitory monoclonal antibody into mammalian cells blocks the rapid effects of insulin, Proc. Natl. Acad. Sci USA 84:41 (1987)
D.G. Baskin, D.P. Figlewicz, S.C. Woods, D. Porte, Jr., and D.M. Dorsa, Insulin in the brain, Ann. Rev. Physiol. 49:335 (1987)
K.A. Heidenreich, G. de Vellis, and P.R. Gilmore, Functional properties of the subtype of insulin receptor found on neurons, J. Neuro-chem. 51:878 (1988)
E. Recio-Pinto, M.M. Rechler, and D.N. Ishii, Effects of insulin, insulin-like growth factor II, nerve growth factor on neurite formation and survival in cultured sympathetic and sensory neurons, J. Neurosci. 6:1211 (1986)
K.A. Heidenreich and S.P. Toledo, Insulin receptors mediate growth effects in cultured fetal neurons. I. Rapid stimulation of protein synthesis, Endocrinology 125:1451 (1989)
J.F. Mill, M.V. Chao, and D.N. Ishii, Insulin, insulin-like growth factor II, and nerve growth factor effects on tubulin mRNA levels and neurite formation, Proc. Natl. Sci. USA 82:7126 (1985)
D.G. Puro and E. Agardh, Insulin-mediated regulation of neuronal maturation, Science 225:1170 (1984)
K.A. Heidenreich, N.R. Zahniser, P. Berhanu, D. Brandenburg, and J. M. Olefsky, Structural differences between insulin receptors in the brain and peripheral target tissues, J. Biol. Chem. 285:8527 (1983)
K.A. Hendenreich and D. Brandenberg, Oligosaccharide heterogeneity of insulin receptors. Comparison of N-linked glycosylation of insulin receptors in adipocytes and brain, Endocrinology 118:1835 (1986)
R.W. Rees-Jones, S.A. Hendricks, M. Quarum, and J. Roth, The insulin receptors of rat brain are coupled to tyrosine kinase activity, J. Biol. Chem. 259:3470 (1984)
K.A. Kenner and K.A. Heidenreich, Regulation of tyrosine phosphorylation by insulin and IGF-I in cultured fetal neurons, Soc. Neurosci. 15:708 (1989)
K.A. Kenner and K.A. Heidenreich, Tyrosine phosphorylation of a 70kDa protein by insulin and insulin-like growth factors in cultured fetal neurons, Soc. Neurosci. 16: (1990)
K.A. Heidenreich, and S.P. Toledo, Insulin receptors mediate growth effects in cultured fetal neurons. II. Activation of a protein kinase that phosphorylates ribosomal protein S6, Endocrinology 125:1458 (1989)
R.H. Chen and J. Blenis, Identification of Xenopus S6 protein kinase homologs (pp90rsk) in somatic cells: Phosphorylation and activation during initial cell proliferation, Mol. Cell. Biol. 10:3204 (1990)
K.A. Heidenreich and S.P. Toledo, Insulin increases protein kinase C activity in both cytosolic and membrane fraction of cultured fetal neurons, Diabetes (Suppl. 1):65A (1989)
K.A. Heidenreich, S.P. Toledo, L.L. Brunton, M.J. Watson, S. Daniel-Issakani, and B. Strulovici, Insulin stimulates the activity of a novel protein kinase C, PKC ε, in cultured fetal chick neurons, J. Biol. Chem. 265:15076 (1990)
D. Schapp and P.J. Parker, Expression, purification, and characterization of protein kinase C-epsilon, J. Biol. Chem. 265:7301 (1990)
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© 1991 Plenum Press, New York
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Heidenreich, K.A., Toledo, S.P., Kenner, K.A. (1991). Regulation of Protein Phosphorylation by Insulin and Insulin-Like Growth Factors in Cultured Fetal Neurons. In: Raizada, M.K., LeRoith, D. (eds) Molecular Biology and Physiology of Insulin and Insulin-Like Growth Factors. Advances in Experimental Medicine and Biology, vol 293. Springer, Boston, MA. https://doi.org/10.1007/978-1-4684-5949-4_33
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DOI: https://doi.org/10.1007/978-1-4684-5949-4_33
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