Phosphorylation activates the insulin receptor tyrosine protein kinase

O. M. Rosen, R. Herrera, Y. Olowe, L. M. Petruzzelli, M. H. Cobb

Research output: Contribution to journalArticle

293 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)3237-3240
Number of pages4
JournalProceedings of the National Academy of Sciences of the United States of America
Volume80
Issue number11 I
StatePublished - 1983

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Insulin Receptor
Phosphorylation
Protein Kinases
Insulin
Wheat Germ Agglutinins
Trypsin Inhibitors
Divalent Cations
Soybeans
Adipocytes
Sepharose
Placenta
Tyrosine
Sucrose
Adenosine Triphosphate
Peptides
Proteins

ASJC Scopus subject areas

  • Genetics
  • General

Cite this

Phosphorylation activates the insulin receptor tyrosine protein kinase. / Rosen, O. M.; Herrera, R.; Olowe, Y.; Petruzzelli, L. M.; Cobb, M. H.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 80, No. 11 I, 1983, p. 3237-3240.

Research output: Contribution to journalArticle

Rosen, O. M. ; Herrera, R. ; Olowe, Y. ; Petruzzelli, L. M. ; Cobb, M. H. / Phosphorylation activates the insulin receptor tyrosine protein kinase. In: Proceedings of the National Academy of Sciences of the United States of America. 1983 ; Vol. 80, No. 11 I. pp. 3237-3240.
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