Phosphorylation of the insulin receptor by a casein kinase I-like enzyme.
A serine protein kinase that phosphorylates the beta-subunit of the insulin receptor has been partially purified 5,000-fold from HeLa cell membranes. The enzyme has been purified by ion-exchange and hydroxylapatite chromatography and sucrose gradient centrifugation; it has an apparent molecular weight of 36,000-43,000 daltons. It exhibits the following properties: (a) it catalyzes the phosphorylation of the autophosphorylated insulin receptor more efficiently than the nonautophosphorylated insulin receptor, (b) it decreases insulin receptor phosphorylation of tubulin but has no effect on insulin receptor phosphorylation of microtubule-associated proteins or reduced and carboxyamidomethylated lysozyme. The enzyme also phosphorylates casein and ribosomal protein S6 and shares many properties with casein kinase I: (a) similar molecular weight, (b) utilization of ATP but not GTP as phosphoryl donor, and (c) sensitivity to inhibition by heparin. Based on several criteria the receptor serine kinase is neither protein kinase C nor the cAMP-dependent protein kinase.
Rapuano
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Memorial Sloan-Kettering Cancer Center, New York, New York 10021.
Rosen
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D000818:Animals; D047388:Casein Kinases; D002460:Cell Line; D002712:Chlorides; D002845:Chromatography; D002852:Chromatography, Ion Exchange; D003600:Cytosol / Q000201:enzymology; D017886:Durapatite; D005260:Female; D006367:HeLa Cells / Q000201:enzymology; D006801:Humans; D006882:Hydroxyapatites; D007700:Kinetics; D008345:Manganese / Q000494:pharmacology; D017895:Manganese Compounds; D051379:Mice; D008970:Molecular Weight; D010766:Phosphorylation; D010920:Placenta / Q000378:metabolism; D011247:Pregnancy; D011494:Protein Kinases / Q000302:isolation & purification / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases; D011972:Receptor, Insulin / Q000302:isolation & purification / Q000378:metabolism*; D012969:Sodium Fluoride / Q000494:pharmacology; D013379:Substrate Specificity
D002712:Chlorides; D006882:Hydroxyapatites; D017895:Manganese Compounds; D008345:Manganese; D012969:Sodium Fluoride; D017886:Durapatite; D011494:Protein Kinases; D011972:Receptor, Insulin; D047388:Casein Kinases; D017346:Protein Serine-Threonine Kinases; C025340:manganese chloride