Insulin and insulin-like growth factor-I stimulate a common endogenous phosphoprotein substrate (pp185) in intact neuroblastoma cells.
Mouse neuroblastoma N18 cells contain specific high affinity insulin and insulin-like growth factor-I (IGF-I) receptors. Insulin and IGF-I induce phosphorylation, in intact cells, of their respective receptor beta subunits. The insulin receptor beta subunit is represented by a 95-kDa phosphoprotein that is recognized by a specific antiserum (B10). The IGF-I receptor beta subunit is represented by two phosphoproteins of molecular mass 95 and 105 kDa. The hormone-induced phosphorylation was rapid and dose-dependent occurring on both phosphoserine and phosphotyrosine residues. In addition, both insulin and IGF-I induced phosphorylation of an endogenous protein of molecular mass 185 kDa (pp185). The rapidity and dose dependency of the phosphorylation of pp185 suggested that it may represent a common endogenous substrate for the insulin and IGF-I receptors in these neural-derived cells. Phosphorylation was primarily on phosphoserine and phosphotyrosine residues. pp185 did not absorb to wheat germ agglutinin-agarose and was not stimulated by either epidermal growth factor or platelet-derived growth factor. The finding of pp185 in these neural-related cells as well as in non-neural tissues suggests that it may represent a ubiquitous endogenous substrate for both the insulin and IGF-I receptor kinases.
D000818:Animals; D002460:Cell Line / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004815:Epidermal Growth Factor / Q000378:metabolism; D007328:Insulin / Q000494:pharmacology*; D007700:Kinetics; D051379:Mice; D008970:Molecular Weight; D009447:Neuroblastoma / Q000378:metabolism*; D010750:Phosphoproteins / Q000378:metabolism*; D010982:Platelet-Derived Growth Factor / Q000378:metabolism; D011972:Receptor, Insulin / Q000378:metabolism; D017451:Receptors, Somatomedin; D013002:Somatomedins / Q000494:pharmacology*
D007328:Insulin; D010750:Phosphoproteins; D010982:Platelet-Derived Growth Factor; D017451:Receptors, Somatomedin; D013002:Somatomedins; D004815:Epidermal Growth Factor; D011972:Receptor, Insulin