Insulin-activated tyrosine phosphorylation of a 15-kilodalton protein in intact 3T3-L1 adipocytes.
Insulin stimulates phosphorylation of a tyrosine residue(s) on a 15-kDa protein (p15), and the cytosolic phosphorylated protein (pp15) accumulates only when 3T3-L1 adipocytes are treated with phenylarsine oxide. It has been shown previously that phenylarsine oxide, an agent that complexes vicinal dithiols, interrupts signal transmission from the insulin receptor to the glucose transport system. Several lines of evidence presented here indicate the involvement of pp15 in insulin receptor-initiated signal transduction to the glucose transport system. The reciprocal effects of phenylarsine oxide on the insulin-activated accumulation of pp15 and on insulin-stimulated hexose uptake are reversed by the vicinal dithiol 2,3-dimercaptopropanol but not by the monothiol 2-mercaptoethanol. Thus, a cellular dithiol appears to function in the signal transmission pathway downstream from pp15. Like the insulin-activated autophosphorylation of the receptor's beta subunit (on tyrosine), activation of phosphorylation of p15 is specific, with insulin-like growth factors 1 and 2, epidermal growth factor, and platelet-derived growth factor being inactive. Moreover, both processes exhibit identical insulin concentration dependence. The temporal kinetic relationship of insulin-activated receptor beta-subunit phosphorylation, followed by the phosphorylation of p15 and then increased hexose uptake rate, is consistent with an intermediary signaling role for pp15 in insulin-stimulated glucose uptake.
D000273:Adipose Tissue / Q000166:cytology / Q000378:metabolism*; D000818:Animals; D001152:Arsenicals / Q000494:pharmacology; D002478:Cells, Cultured; D004789:Enzyme Activation; D007328:Insulin / Q000494:pharmacology*; D007700:Kinetics; D051379:Mice; D008970:Molecular Weight; D010761:Phosphorus Radioisotopes; D010766:Phosphorylation; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D011506:Proteins / Q000378:metabolism*; D011972:Receptor, Insulin / Q000378:metabolism*
D001152:Arsenicals; D007328:Insulin; D010761:Phosphorus Radioisotopes; D011506:Proteins; C029341:oxophenylarsine; D011505:Protein-Tyrosine Kinases; D011972:Receptor, Insulin