Atypical protein kinase C (PKCzeta/lambda) is a convergent downstream target of the insulin-stimulated phosphatidylinositol 3-kinase and TC10 signaling pathways

J Cell Biol. 2004 Jan 19;164(2):279-90. doi: 10.1083/jcb.200306152.

Abstract

Insulin stimulation of adipocytes resulted in the recruitment of atypical PKC (PKCzeta/lambda) to plasma membrane lipid raft microdomains. This redistribution of PKCzeta/lambda was prevented by Clostridium difficile toxin B and by cholesterol depletion, but was unaffected by inhibition of phosphatidylinositol (PI) 3-kinase activity. Expression of the constitutively active GTP-bound form of TC10 (TC10Q/75L), but not the inactive GDP-bound mutant (TC10/T31N), targeted PKCzeta/lambda to the plasma membrane through an indirect association with the Par6-Par3 protein complex. In parallel, insulin stimulation as well as TC10/Q75L resulted in the activation loop phosphorylation of PKCzeta. Although PI 3-kinase activation also resulted in PKCzeta/lambda phosphorylation, it was not recruited to the plasma membrane. Furthermore, insulin-induced GSK-3beta phosphorylation was mediated by both PI 3-kinase-PKB and the TC10-Par6-atypical PKC signaling pathways. Together, these data demonstrate that PKCzeta/lambda can serve as a convergent downstream target for both the PI 3-kinase and TC10 signaling pathways, but only the TC10 pathway induces a spatially restricted targeting to the plasma membrane.

Publication types

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

MeSH terms

  • 3T3 Cells
  • Adipocytes / cytology
  • Adipocytes / physiology*
  • Animals
  • Cell Fractionation
  • Cell Membrane / metabolism
  • Insulin / pharmacology*
  • Isoenzymes
  • Mice
  • Phosphatidylinositol 3-Kinases / metabolism*
  • Protein Kinase C / metabolism*
  • Protein Transport
  • Substrate Specificity
  • rho GTP-Binding Proteins / metabolism*

Substances

  • Insulin
  • Isoenzymes
  • Phosphatidylinositol 3-Kinases
  • protein kinase C zeta
  • Protein Kinase C
  • protein kinase C lambda
  • Rhoq protein, mouse
  • rho GTP-Binding Proteins