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Phosphorylation Activates the Insulin Receptor Tyrosine Protein Kinase
Ora M. Rosen, Roman Herrera, Yetunde Olowe, Lilli M. Petruzzelli and Melanie H. Cobb
Proceedings of the National Academy of Sciences of the United States of America
Vol. 80, No. 11, [Part 1: Biological Sciences] (Jun. 1, 1983), pp. 3237-3240
Published by: National Academy of Sciences
Stable URL: http://www.jstor.org/stable/14506
Page Count: 4
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Preparations of insulin receptor from cultured 3T3-L1 adipocytes and human placenta previously was found to catalyze the phosphorylation of the 90,000-dalton component of the insulin receptor on tyrosine residues. This insulin-dependent phosphorylation has now been shown to coincide with the generation of an activated, insulin-independent, receptor protein kinase. Activation is dependent upon ATP, divalent cations (Mg2+ and Mn2+), and insulin (half-maximal activation occurs at 6-8 nM insulin). The time required for activation is consistent with that needed for insulin-dependent self-phosphorylation of the receptor present in eluates from wheat germ lectin-agarose columns and in preparations of affinity-purified placental receptor. Activation proceeds unabated in the presence of soybean trypsin inhibitor at 0.1 mg/ml and the activated, insulin-independent, protein kinase sediments in 5-20% sucrose gradients at the same position as the unmodified receptor. Under steady-state conditions, the phosphorylated receptor binds insulin in the same fashion as the unmodified receptor. It is proposed that the self-phosphorylated form of the receptor is the insulin-activated protein kinase that catalyzes the phosphorylation of exogenous protein and peptide substrates. A corollary of this hypothesis is that enzymatic dephosphorylation may be essential for reversibly terminating the activity of the insulin-receptor protein kinase.
Proceedings of the National Academy of Sciences of the United States of America © 1983 National Academy of Sciences