Activation of protein kinase C alpha inhibits insulin-stimulated tyrosine phosphorylation of insulin receptor substrate-1

Mol Endocrinol. 1994 Jan;8(1):51-8. doi: 10.1210/mend.8.1.7512195.

Abstract

Chinese hamster ovary (CHO) cells were transfected with a cDNA encoding protein kinase C alpha (PKC) and a cell line (CHO-PKC alpha) expressing approximately 7-fold greater amounts of PKC as the parental cells were isolated. Activation of PKC by 12-O-tetradecanoylphorbol-13-acetate in the CHO-PKC alpha cells inhibited by approximately 75% the: 1) insulin-stimulated increase in antiphosphotyrosine precipitable phosphatidylinositol 3-kinase activity in these cells; 2) insulin-stimulated increase in PI 3-kinase activity associated with insulin receptor substrate-1; and 3) tyrosine phosphorylation of the endogenous substrate, insulin receptor substrate-1. In contrast, 12-O-tetradecanoylphorbol-13-acetate treatment did not inhibit any of these responses in the parental CHO cells. These results indicate that excessive PKC activity can interfere in a very early step in insulin receptor signaling and are consistent with the hypothesis that excessive PKC activity may contribute to some states of insulin resistance.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Blotting, Western
  • CHO Cells
  • Cricetinae
  • DNA, Complementary / genetics
  • Enzyme Activation
  • Immunosorbent Techniques
  • Insulin / pharmacology*
  • Insulin Receptor Substrate Proteins
  • Phosphatidylinositol 3-Kinases
  • Phosphoproteins / metabolism*
  • Phosphorylation
  • Phosphotransferases (Alcohol Group Acceptor) / antagonists & inhibitors
  • Phosphotransferases (Alcohol Group Acceptor) / metabolism
  • Phosphotyrosine
  • Protein Kinase C / genetics
  • Protein Kinase C / metabolism*
  • Signal Transduction
  • Tetradecanoylphorbol Acetate / pharmacology
  • Transfection
  • Tyrosine / analogs & derivatives*
  • Tyrosine / metabolism

Substances

  • DNA, Complementary
  • Insulin
  • Insulin Receptor Substrate Proteins
  • Phosphoproteins
  • Phosphotyrosine
  • Tyrosine
  • Phosphatidylinositol 3-Kinases
  • Phosphotransferases (Alcohol Group Acceptor)
  • Protein Kinase C
  • Tetradecanoylphorbol Acetate