Mutation of the insulin receptor at tyrosine 960 inhibits signal transmission but does not affect its tyrosine kinase activity

Morris F. White, James N. Livingston, Jonathan M. Backer, Vilma Lauris, Thomas J. Dull, Axel Ullrich, C. Ronald Kahn

Research output: Contribution to journalArticle

262 Citations (Scopus)

Abstract

Tyrosyl phosphorylation is implicated in the mechanism of insulin action. Mutation of the β-subunit of the insulin receptor by substitution of tyrosyl residue 960 with phenylalanine had no effect on insulin-stimulated autophosphorylation or phosphotransferase activity of the purified receptor. However, unlike the normal receptor, this mutant was not biologically active in Chinese hamster ovary cells. Furthermore, insulin-stimulated tyrosyl phosphorylation of at least one endogenous substrate (pp185) was increased significantly in cells expressing the normal receptor but was barely detected in cells expressing the mutant. Therefore, β-subunit autophosphorylation was not sufficient for the insulin response, and a region of the insulin receptor around Tyr-960 may facilitate phosphorylation of cellular substrates required for transmission of the insulin signal.

Original languageEnglish (US)
Pages (from-to)641-649
Number of pages9
JournalCell
Volume54
Issue number5
DOIs
StatePublished - Aug 26 1988
Externally publishedYes

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Insulin Receptor
Protein-Tyrosine Kinases
Tyrosine
Phosphorylation
Insulin
Mutation
Cells
Substrates
Cricetulus
Phenylalanine
Ovary
Substitution reactions
Phosphotransferases

ASJC Scopus subject areas

  • Cell Biology
  • Molecular Biology

Cite this

Mutation of the insulin receptor at tyrosine 960 inhibits signal transmission but does not affect its tyrosine kinase activity. / White, Morris F.; Livingston, James N.; Backer, Jonathan M.; Lauris, Vilma; Dull, Thomas J.; Ullrich, Axel; Kahn, C. Ronald.

In: Cell, Vol. 54, No. 5, 26.08.1988, p. 641-649.

Research output: Contribution to journalArticle

White, Morris F. ; Livingston, James N. ; Backer, Jonathan M. ; Lauris, Vilma ; Dull, Thomas J. ; Ullrich, Axel ; Kahn, C. Ronald. / Mutation of the insulin receptor at tyrosine 960 inhibits signal transmission but does not affect its tyrosine kinase activity. In: Cell. 1988 ; Vol. 54, No. 5. pp. 641-649.
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