title: Substrates for insulin-receptor kinase.
abstract: Several studies suggest that the tyrosine-specific protein kinase activity of the beta-subunit of the insulin receptor is necessary to mediate the biological effects of insulin. This conclusion leads to the hypothesis that the effect of insulin is mediated through the tyrosine phosphorylation of cellular substrates by the insulin-receptor tyrosine kinase. In this review, the experimental evidence regarding insulin-stimulated phosphorylation of proteins both in vitro and in vivo is evaluated. In a cell-free system, tubulin, microtubule-associated protein 2, tau, fodrin, calmodulin-dependent kinase, calmodulin, and lipocortins 1 and 2 were reported to be good substrates for insulin-receptor kinase. However, none were found to be tyrosine phosphorylated in an intact-cell system. In intact-cell systems, proteins of Mr 185,000 (pp185), 120,000 (pp120), 240,000 (pp240), 15,000 (pp15), 60,000 (pp60), and 62,000 (pp62) as well as several others were reported to be tyrosine phosphorylated in an insulin-dependent fashion. However, the function or functional alteration of these proteins induced by insulin-stimulated tyrosine phosphorylation is not clear. Therefore, physiologically relevant substrates for the insulin-receptor kinase have not been established, and more work is necessary to verify the phosphorylation cascade hypothesis of insulin action.
authors.affiliation: Third Department of Internal Medicine, University of Tokyo, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Kasuga
authors.forename: T
authors.initials: T
authors.lastname: Izumi
authors.forename: K
authors.initials: K
authors.lastname: Tobe
authors.forename: T
authors.initials: T
authors.lastname: Shiba
authors.forename: K
authors.initials: K
authors.lastname: Momomura
authors.forename: Y
authors.initials: Y
authors.lastname: Tashiro-Hashimoto
authors.forename: T
authors.initials: T
authors.lastname: Kadowaki
mesh_terms: D000818:Animals; D002462:Cell Membrane / Q000378:metabolism; D006801:Humans; D008961:Models, Structural; D010766:Phosphorylation; D011487:Protein Conformation; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D011972:Receptor, Insulin / Q000378:metabolism*; D013379:Substrate Specificity
chemical_list: D011505:Protein-Tyrosine Kinases; D011972:Receptor, Insulin