Various proteins modulate the kinase activity of the insulin receptor.
Previous studies of the substrate specificity of the purified insulin receptor tyrosine kinase using synthetic random polymers have demonstrated that the receptor kinase phosphorylates poly (Glu, Tyr) 4:1 but not poly (Glu, Tyr) 1:1. In the present study, insulin treatment of Chinese hamster ovary cells overexpressing the human insulin receptor was found to stimulate the ability of their membrane extracts to phosphorylate poly (Glu, Tyr) 1:1. It was concluded that this activity was due to the receptor itself because: 1) it was precipitated with a monoclonal antibody to the receptor; 2) the addition of various membrane extracts to purified insulin receptor preparations stimulated the ability of these preparations to phosphorylate poly (Glu, Tyr) 1:1; and 3) certain purified proteins, including bovine serum albumin and casein, were also capable of stimulating the purified receptor to phosphorylate poly (Glu, Tyr) 1:1. The effect of albumin was dose-dependent; 0.5 and 10 mg/ml bovine serum albumin stimulated the phosphorylation of poly (Glu, Tyr) 1:1 by 2- and 230-fold, respectively. In contrast, albumin had no effect on the phosphorylation of poly (Glu, Tyr) 4:1. These results indicate that the activity of the insulin receptor kinase on certain substrates can be modulated by the presence of other proteins.
Yonezawa
K
K
Department of Pharmacology, Stanford University School of Medicine, California 94305.
Roth
R A
RA
D000818:Animals; D002364:Caseins / Q000494:pharmacology; D002460:Cell Line; D002462:Cell Membrane / Q000187:drug effects / Q000201:enzymology; D006224:Cricetinae; D007163:Immunosorbent Techniques; D007328:Insulin / Q000494:pharmacology; D036341:Intercellular Signaling Peptides and Proteins; D010455:Peptides / Q000378:metabolism; D010766:Phosphorylation; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D011506:Proteins / Q000494:pharmacology*; D011972:Receptor, Insulin; D012710:Serum Albumin, Bovine / Q000494:pharmacology
D002364:Caseins; D007328:Insulin; D036341:Intercellular Signaling Peptides and Proteins; D010455:Peptides; D011506:Proteins; D012710:Serum Albumin, Bovine; C027606:L-glutamic acid-L-tyrosine copolymer; D011505:Protein-Tyrosine Kinases; D011972:Receptor, Insulin