INSULIN-RECEPTOR HAS TYROSINE KINASE-ACTIVITY TOWARD SHC IN RAT-LIVER

Insulin induces tyrosine phosphorylation of Shc in cell cultures and i n insulin-sensitive tissues of the intact rat. However, the ability of insulin receptor (IR) tyrosine kinase to phosphorylate Shc has not be en previously demonstrated. In the present study, we investigated insu lin-induced IR tyrosine kinase activity towards Shc. Insulin receptor was immunoprecipitated from liver extracts, before and after a very lo w dose of insulin into the portal vein, and incubated with immunopurif ied Shc from liver of untreated rats. The kinase assay was performed i n vitro in the presence of exogenous ATP and the phosphorylation level was quantified by immunoblotting with antiphosphotyrosine antibody. T he results demonstrate that Shc interacted with insulin receptor after infusion of insulin, and, more important, there was insulin receptor kinase activity towards immunopurified Shc. The description of this pa thway in animal tissue may have an important role in insulin receptor tyrosine kinase activity toward mitogenic transduction pathways.