JNK/SAPK activation by platelet-derived growth factor in A431 cells requires both the phospholipase C-gamma and the phosphatidylinositol 3-kinase signaling pathways of the receptor

Biochem Biophys Res Commun. 1999 Aug 11;261(3):641-5. doi: 10.1006/bbrc.1999.1090.

Abstract

Wild-type or mutant betaPDGF receptors were introduced into A431 cells that lack endogenous PDGF receptors. PDGF stimulates JNK1 activity in a dose- and time-dependent manner in cells expressing the wild-type receptor. A receptor mutant lacking all the binding sites for SHP-2, GAP, PI3K, and PLC-gamma fails to activate JNK1. Receptor mutants with no binding site for either SHP-2 or GAP can fully activate JNK1 but those which do not bind either PI3K or PLC-gamma are unable to induce JNK1 activation. PDGF-dependent JNK1 activation was reduced upon cell pretreatment with wortmannin or GF109203X and is completely abrogated by chronic PMA stimulation. Altogether, these results indicate that PDGF activates JNK1 through a pathway that involves both PI3K and PLC-gamma and subsequent activation of protein kinase C.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Androstadienes / pharmacology
  • Binding Sites
  • Calcium-Calmodulin-Dependent Protein Kinases / metabolism*
  • Cell Line
  • Enzyme Activation
  • Enzyme Inhibitors / pharmacology
  • JNK Mitogen-Activated Protein Kinases
  • Mitogen-Activated Protein Kinases*
  • Mutation
  • Phosphatidylinositol 3-Kinases / metabolism*
  • Phosphoinositide-3 Kinase Inhibitors
  • Platelet-Derived Growth Factor / pharmacology*
  • Protein Kinase C / antagonists & inhibitors
  • Receptors, Platelet-Derived Growth Factor / genetics
  • Receptors, Platelet-Derived Growth Factor / metabolism*
  • Signal Transduction*
  • Tetradecanoylphorbol Acetate / pharmacology
  • Type C Phospholipases / metabolism*
  • Wortmannin

Substances

  • Androstadienes
  • Enzyme Inhibitors
  • Phosphoinositide-3 Kinase Inhibitors
  • Platelet-Derived Growth Factor
  • Receptors, Platelet-Derived Growth Factor
  • Protein Kinase C
  • Calcium-Calmodulin-Dependent Protein Kinases
  • JNK Mitogen-Activated Protein Kinases
  • Mitogen-Activated Protein Kinases
  • Type C Phospholipases
  • Tetradecanoylphorbol Acetate
  • Wortmannin