Phosphatidylinositol 3'-kinase Is Associated With a Serine Kinase That Is Activated by Okadaic Acid

Biochem Biophys Res Commun. 1998 Jan 26;242(3):513-7. doi: 10.1006/bbrc.1997.7996.

Abstract

Okadaic acid (OA) is a potent inhibitor of PP1 and PP2A serine/threonine phosphatases and an inhibitor of phosphatidylinositol 3'-kinase (PI 3-kinase) recruitment/ activation. Here we report that PI 3-kinase associates with a serine kinase activated by OA. Whole cell phosphorylation studies showed that PI 3-kinase associates with a wortmannin insensitive 76 kDa serine phosphoprotein (pp76) distinct from the p85 subunit of PI 3-kinase. Serine kinase assays demonstrated that pp76 phosphorylation was dependent upon a wortmannin insensitive serine kinase contained within PI 3-kinase/pp76 complexes and that this kinase had different cation requirements than PI 3-kinase serine kinase. Treatment of whole cells with OA lead to a wortmannin-independent 7.6-fold increase in pp76 serine phosphorylation and to a 7-fold rise in pp76 kinase activity. Together, these findings indicate that pp76 is a PI 3-kinase associated phosphoprotein and suggest that pp76 may be a novel PI 3-kinase associated serine kinase that is activated by OA.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Androstadienes / pharmacology
  • Blotting, Western
  • Enzyme Inhibitors / pharmacology
  • Humans
  • Multiple Myeloma
  • Okadaic Acid / pharmacology*
  • Phosphatidylinositol 3-Kinases / metabolism*
  • Phosphoproteins / analysis
  • Phosphoproteins / metabolism
  • Phosphorylation
  • Phosphoserine / metabolism
  • Precipitin Tests
  • Protein-Serine-Threonine Kinases / analysis
  • Protein-Serine-Threonine Kinases / metabolism*
  • Tumor Cells, Cultured
  • Wortmannin

Substances

  • Androstadienes
  • Enzyme Inhibitors
  • Phosphoproteins
  • Phosphoserine
  • Okadaic Acid
  • Phosphatidylinositol 3-Kinases
  • Protein-Serine-Threonine Kinases
  • Wortmannin