Activation of MAP kinase in Swiss 3T3 fibroblasts by insulin-like growth factor-I.
A peak of cytosolic myelin basic protein kinase activity was observed at 2-5 min after addition of 10 nM insulin-like growth factor-I (IGF-I) to Swiss 3T3 fibroblasts. Analysis of the induced kinase activity by chromatography, immunodetection and in situ kinase assay suggests that this represents a 1.8- to 3.5-fold increase in the activity of p42 mitogen-activated protein kinase. Addition of insulin at 10 nM also resulted in an increased kinase activity in these respects, however, only to approximately 60% of that induced by IGF-I. A similar quantitative relation between the effects of insulin and IGF-I was found for induction of lipid and glycogen synthesis from [14C- (U)]-D-glucose. However, incorporation of 3H-L-leucine into protein was stimulated to the same extent by the two agents. The effect of 10 nM insulin on proliferation, measured as tetrazolium dye reduction, was only 18% of that induced by 10 nM IGF-I. The obtained data suggest that cytosolic mitogen-activated protein kinase activation may constitute a signalling pathway for glucose metabolism, and especially glycogen synthesis, induced by peptides of the insulin superfamily.
Hansson
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A
Department of Molecular Medicine, Karolinska Institutet, Stockholm, Sweden.
Thorén
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M
D016475:3T3 Cells; D000595:Amino Acid Sequence; D000818:Animals; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism*; D002455:Cell Division; D004789:Enzyme Activation; D005947:Glucose / Q000378:metabolism; D006003:Glycogen / Q000096:biosynthesis; D038362:Glycogen Synthase Kinase 3; D007328:Insulin / Q000494:pharmacology; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology*; D008055:Lipids / Q000096:biosynthesis; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D010084:Oxidation-Reduction; D014176:Protein Biosynthesis; D013379:Substrate Specificity; D014316:Tritium
D007328:Insulin; D008055:Lipids; D014316:Tritium; D007334:Insulin-Like Growth Factor I; D006003:Glycogen; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D038362:Glycogen Synthase Kinase 3; D005947:Glucose