Protein kinase C betaII regulates Akt phosphorylation on Ser-473 in a cell type- and stimulus-specific fashion

J Biol Chem. 2004 Nov 12;279(46):47720-5. doi: 10.1074/jbc.M408797200. Epub 2004 Sep 9.

Abstract

Akt (= protein kinase B), a subfamily of the AGC serine/threonine kinases, plays critical roles in survival, proliferation, glucose metabolism, and other cellular functions. Akt activation requires the recruitment of the enzyme to the plasma membrane by interacting with membrane-bound lipid products of phosphatidylinositol 3-kinase. Membrane-bound Akt is then phosphorylated at two sites for its full activation; Thr-308 in the activation loop of the kinase domain is phosphorylated by 3-phosphoinositide-dependent kinase-1 (PDK1) and Ser-473 in the C-terminal hydrophobic motif by a putative kinase PDK2. The identity of PDK2 has been elusive. Here we present evidence that conventional isoforms of protein kinase C (PKC), particularly PKCbetaII, can regulate Akt activity by directly phosphorylating Ser-473 in vitro and in IgE/antigen-stimulated mast cells. By contrast, PKCbeta is not required for Ser-473 phosphorylation in mast cells stimulated with stem cell factor or interleukin-3, in serum-stimulated fibroblasts, or in antigen receptor-stimulated T or B lymphocytes. Therefore, PKCbetaII appears to work as a cell type- and stimulus-specific PDK2.

Publication types

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

MeSH terms

  • Animals
  • Bone Marrow Cells / cytology
  • Bone Marrow Cells / physiology
  • Cells, Cultured
  • Enzyme Activation
  • Immunoglobulin E / pharmacology
  • Interleukin-2 / metabolism
  • Isoenzymes / genetics
  • Isoenzymes / metabolism*
  • Mast Cells / cytology
  • Mast Cells / drug effects
  • Mast Cells / physiology
  • Mice
  • Mice, Knockout
  • Phorbol Esters / pharmacology
  • Phosphorylation
  • Protein Kinase C / genetics
  • Protein Kinase C / metabolism*
  • Protein Kinase C beta
  • Protein Serine-Threonine Kinases / genetics
  • Protein Serine-Threonine Kinases / metabolism*
  • Proto-Oncogene Proteins / genetics
  • Proto-Oncogene Proteins / metabolism*
  • Proto-Oncogene Proteins c-akt
  • Receptors, IgE / metabolism
  • Serine / metabolism*

Substances

  • Interleukin-2
  • Isoenzymes
  • Phorbol Esters
  • Proto-Oncogene Proteins
  • Receptors, IgE
  • Immunoglobulin E
  • Serine
  • Protein Serine-Threonine Kinases
  • Proto-Oncogene Proteins c-akt
  • Protein Kinase C
  • Protein Kinase C beta