The alpha-isoform of class II phosphoinositide 3-kinase is more effectively activated by insulin receptors than IGF receptors, and activation requires receptor NPEY motifs

FEBS Lett. 1999 Nov 5;460(3):423-6. doi: 10.1016/s0014-5793(99)01388-5.

Abstract

Little is known about the physiological role and mechanism of activation of class II phosphoinositide 3-kinases (PI3Ks), although it has been shown that the PI3K-C2alpha isoform is activated by insulin. Using chimaeric receptor constructs which can be activated independently of endogenous receptors in transfected cells, we found that PI3K-C2alpha activity was stimulated to a greater extent by insulin receptors than IGF receptors in 3T3-L1 adipocytes. Activation of PI3K-C2alpha required an intact NPEY motif in the receptor juxtamembrane domain. We conclude that PI3K-C2alpha is a candidate for participation in insulin-specific intracellular signalling.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3T3 Cells / enzymology
  • Adipocytes / enzymology
  • Amino Acid Motifs / genetics
  • Amino Acid Substitution / genetics
  • Animals
  • Cell Line
  • Humans
  • Isoenzymes / physiology*
  • Mice
  • Mutagenesis, Site-Directed / genetics
  • Phenylalanine / genetics
  • Phosphatidylinositol 3-Kinases / physiology*
  • Receptor, IGF Type 1 / biosynthesis
  • Receptor, IGF Type 1 / genetics
  • Receptor, IGF Type 1 / physiology*
  • Receptor, Insulin / genetics
  • Receptor, Insulin / physiology*
  • Recombinant Fusion Proteins / biosynthesis
  • Recombinant Fusion Proteins / genetics
  • Tyrosine / genetics

Substances

  • Isoenzymes
  • Recombinant Fusion Proteins
  • Tyrosine
  • Phenylalanine
  • Phosphatidylinositol 3-Kinases
  • Receptor, IGF Type 1
  • Receptor, Insulin