title: The stimulation of pp42mapkinase by insulin does not correlate with its metabolic actions in cells overexpressing mutant insulin receptors.
abstract: Naturally occurring human insulin receptor mutants Ser1200 and Thr1134, and a site-directed mutant Arg1030 overexpressed in Chinese hamster ovary (CHO) cells, bind insulin with affinities identical to wildtype receptors but are apparently kinase deficient. Cells expressing the Ser1200 receptor exhibit insulin stimulation of glycogen synthesis similar to these bearing the wildtype receptor, but fail to mediate insulin-responsive DNA synthesis. In contrast, the Thr1134 and Arg1030 mutants exhibit no response to insulin. The activity of Mitogen Activated Protein (MAP) kinase in cells transfected with wildtype receptor is more responsive to insulin than that detected in untransfected parental cells, while cells bearing any of the mutant receptors are less responsive than the parental cells. These differences in the stimulation of MAP kinase activity are paralleled by differences in insulin-dependent phosphorylation of the enzyme. These results suggest that the p42 MAP kinase is not universally required for the metabolic effects of insulin.
authors.affiliation: Department of Physiology, University of Michigan, School of Medicine, Ann Arbor 48109.
authors.forename: L
authors.initials: L
authors.lastname: Pang
authors.forename: D F
authors.initials: DF
authors.lastname: Lazar
authors.forename: D E
authors.initials: DE
authors.lastname: Moller
authors.forename: J S
authors.initials: JS
authors.lastname: Flier
authors.forename: A R
authors.initials: AR
authors.lastname: Saltiel
mesh_terms: D000818:Animals; D016466:CHO Cells; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000187:drug effects / Q000378:metabolism*; D006224:Cricetinae; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation / Q000187:drug effects; D006801:Humans; D007328:Insulin / Q000494:pharmacology*; D009154:Mutation; D010766:Phosphorylation; D011972:Receptor, Insulin / Q000096:biosynthesis* / Q000235:genetics; D011994:Recombinant Proteins / Q000096:biosynthesis; D014443:Tyrosine / Q000378:metabolism
chemical_list: D007328:Insulin; D011994:Recombinant Proteins; D014443:Tyrosine; D011972:Receptor, Insulin; D017871:Calcium-Calmodulin-Dependent Protein Kinases