PDGF-dependent tyrosine phosphorylation stimulates production of novel polyphosphoinositides in intact cells

Cell. 1989 Apr 7;57(1):167-75. doi: 10.1016/0092-8674(89)90182-7.


A phosphatidylinositol (PI) kinase activity associated with certain protein tyrosine kinases important in cell proliferation phosphorylates the 3' hydroxyl position of PI to produce phosphatidylinositol-3-phosphate (PI-3-P). Here we report that, in addition to PI-3' kinase activity, anti-phosphotyrosine (alpha-P-tyr) immunoprecipitates from platelet-derived growth factor (PDGF)-stimulated smooth muscle cells (SMC) contain lipid kinase activities that utilize the substrates phosphatidylinositol-4-phosphate (PI-4-P) and phosphatidylinositol-4,5-bisphosphate (PI-4,5-P2). These activities are absent in alpha-P-tyr immunoprecipitates from quiescent SMC. The product of PI-4-P phosphorylation appears to be phosphatidylinositol-3,4-bisphosphate (PI-3,4-P2), a lipid not previously reported. The product of PI-4,5-P2 phosphorylation is phosphatidylinositol-trisphosphate (PIP3). PI-3-P was detected in quiescent SMC and increased only slightly in response to PDGF. PIP3 and the putative PI-3,4-P2 appeared only after the addition of mitogen. Both the temporal production of these novel phospholipids after PDGF stimulation and the observation of the enzymatic activities that produce them in alpha-P-tyr immunoprecipitates suggest that these phospholipids are excellent candidates for mediators of the PDGF mitogenic response.

Publication types

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

MeSH terms

  • 1-Phosphatidylinositol 4-Kinase
  • Calcium / pharmacology
  • Gene Expression Regulation
  • Humans
  • Inositol Phosphates / analysis
  • Mitosis / drug effects
  • Muscle, Smooth, Vascular / cytology*
  • Muscle, Smooth, Vascular / drug effects
  • Muscle, Smooth, Vascular / enzymology
  • Phosphatidylinositol Phosphates
  • Phosphatidylinositols / analysis
  • Phosphatidylinositols / metabolism*
  • Phosphatidylinositols / physiology
  • Phosphorylation
  • Phosphotransferases / metabolism
  • Phosphotyrosine
  • Platelet-Derived Growth Factor / pharmacology*
  • Platelet-Derived Growth Factor / physiology
  • Precipitin Tests
  • Protein-Tyrosine Kinases / metabolism*
  • Receptors, Cell Surface / metabolism
  • Receptors, Platelet-Derived Growth Factor
  • Tyrosine / analogs & derivatives
  • Tyrosine / immunology


  • Inositol Phosphates
  • Phosphatidylinositol Phosphates
  • Phosphatidylinositols
  • Platelet-Derived Growth Factor
  • Receptors, Cell Surface
  • Phosphotyrosine
  • Tyrosine
  • Phosphotransferases
  • 1-Phosphatidylinositol 4-Kinase
  • Protein-Tyrosine Kinases
  • Receptors, Platelet-Derived Growth Factor
  • Calcium