title: Mutation of the insulin receptor at tyrosine 960 inhibits signal transmission but does not affect its tyrosine kinase activity.
abstract: Tyrosyl phosphorylation is implicated in the mechanism of insulin action. Mutation of the beta-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, beta-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.
authors.affiliation: Joslin Diabetes Center, Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts 02215.
authors.forename: M F
authors.initials: MF
authors.lastname: White
authors.forename: J N
authors.initials: JN
authors.lastname: Livingston
authors.forename: J M
authors.initials: JM
authors.lastname: Backer
authors.forename: V
authors.initials: V
authors.lastname: Lauris
authors.forename: T J
authors.initials: TJ
authors.lastname: Dull
authors.forename: A
authors.initials: A
authors.lastname: Ullrich
authors.forename: C R
authors.initials: CR
authors.lastname: Kahn
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D002460:Cell Line; D003001:Cloning, Molecular; D004247:DNA / Q000235:genetics; D005796:Genes; D006801:Humans; D007700:Kinetics; D008969:Molecular Sequence Data; D009154:Mutation; D010766:Phosphorylation; D011505:Protein-Tyrosine Kinases / Q000235:genetics* / Q000378:metabolism; D011972:Receptor, Insulin; D014162:Transfection; D014443:Tyrosine
chemical_list: D014443:Tyrosine; D004247:DNA; D011505:Protein-Tyrosine Kinases; D011972:Receptor, Insulin