Evidence for insulin-dependent activation of S6 and microtubule-associated protein-2 kinases via a human insulin receptor/v-ros hybrid

Teri G. Boulton, Jill S. Gregory, Song Muh Jong, Lu Hai Wang, Leland Ellis, Melanie H. Cobb

Research output: Contribution to journalArticle

24 Scopus citations

Abstract

The abilities of a series of six mutants of the human insulin receptor, and insulin receptor/v-ros hybrid (IRros) and the P68(gag-ros) transforming protein to stimulate S6 protein kinase kinase have been assessed. Insulin receptor mutants in which either 1 or 2 tyrosine residues have been replaced with phenylalanine (YF1, YF3) have lost some or all of the capacity to mediate the activation of S6 kinase in response to insulin. None of the four mutants that contain deletions (spBam, spBamYF3, iBgl, T-t) elicit an insulin-dependent stimulation of S6 kinase. A previous study of the IRros hybrid receptor demonstrated that it was unable to cause either insulin-stimulated thymidine incorporation or glucose uptake (Ellis, L., Morgan, D.O., Jong, S.-M., Wang, L.-H., Roth, R.A., and Rutter, W.J. (1987) Proc. Natl. Acad. Sci. U.S.A. 84, 5101-5105). In contrast, the IRros chimera appears to mediate the activation of S6 protein kinase by insulin. In further evaluating the biological activities of the IRros hybrid, we have examined its effects on a microtubule-associated protein-2 (MAP2) kinase that is thought to be an early target in the cascade of reactions leading to increased S6 phosphorylation (Sturgill, T.W., Ray, L.B., Erickson, E., and Maller, J.L. (1988) Nature 334, 715-718). We find that the IRros receptor stimulates the MAP2 protein kinase from 3- to 6-fold in insulin-treated cells, conferring more than a 30-fold increase in the insulin sensitivity of MAP2 kinase activation.

Original languageEnglish (US)
Pages (from-to)2713-2719
Number of pages7
JournalJournal of Biological Chemistry
Volume265
Issue number5
StatePublished - Apr 2 1990

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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