Activation of phosphoinositide 3-kinase is required for PDGF-stimulated membrane ruffling

Curr Biol. 1994 May 1;4(5):385-93. doi: 10.1016/s0960-9822(00)00087-7.


Background: There is substantial evidence that phosphoinositide 3-kinase (PI 3-kinase) is a critical component of signalling pathways used by the cell-surface receptors for a variety of mammalian growth factors and other hormones. The physiological product of this enzyme is a highly polar membrane lipid called phosphatidylinositol (3,4,5)-trisphosphate This lipid has been postulated to act as a second-messenger in cells but its putative targets are still unknown.

Results: A particular rearrangement of actin filaments, which results in membrane ruffling, is elicited by the activation of PDGF beta-receptors expressed in cultured porcine aortic endothelial cells. We have found that this consequence of PDGF beta-receptor activation is inhibited by three independent manipulations of PI 3-kinase activity: firstly, by the deletion of tyrosine residues in the PDGF beta-receptor to which PI 3-kinase binds; secondly, by the overexpression of a mutant 85 kD PI 3-kinase regulatory subunit to which the catalytic kinase subunit cannot bind; and thirdly, by the addition of the fungal metabolite wortmannin, which is a potent inhibitor of the catalytic activity of PI 3-kinase.

Conclusions: These results argue strongly that phosphatidylinositol (3,4,5)-trisphosphate synthesis is required for growth-factor-stimulated membrane ruffling in porcine aortic endothelial cells, and suggest that synthesis of this lipid may be part of a signalling pathway leading to direct or indirect activation of the small GTP-binding protein Rac.

MeSH terms

  • Androstadienes / pharmacology
  • Animals
  • Binding Sites / genetics
  • Cell Line
  • Cell Membrane / drug effects*
  • Cell Membrane / metabolism
  • Cell Membrane / ultrastructure
  • Enzyme Activation
  • Models, Biological
  • Mutation
  • Phosphatidylinositol 3-Kinases
  • Phosphatidylinositol Phosphates / biosynthesis
  • Phosphorylation
  • Phosphotransferases (Alcohol Group Acceptor) / metabolism*
  • Platelet-Derived Growth Factor / pharmacology*
  • Receptors, Platelet-Derived Growth Factor / genetics
  • Receptors, Platelet-Derived Growth Factor / metabolism
  • Signal Transduction
  • Swine
  • Wortmannin


  • Androstadienes
  • Phosphatidylinositol Phosphates
  • Platelet-Derived Growth Factor
  • phosphatidylinositol 3,4,5-triphosphate
  • Phosphatidylinositol 3-Kinases
  • Phosphotransferases (Alcohol Group Acceptor)
  • Receptors, Platelet-Derived Growth Factor
  • Wortmannin