Platelet-derived growth factor stimulates synthesis of PtdIns(3,4,5)P3 by activating a PtdIns(4,5)P2 3-OH kinase

Nature. 1992 Jul 9;358(6382):157-9. doi: 10.1038/358157a0.


Although the hormone-stimulated synthesis of 3-phosphorylated inositol lipids is known to form an intracellular signalling system, there is no consensus on the crucial receptor-regulated event in this pathway and it is still not clear which of the intermediates represent potential output signals. We show here that the key step in the synthesis of 3-phosphorylated inositol lipids in 3T3 cells stimulated by platelet-derived growth factor is the activation of a phosphatidylinositol(4,5)-bisphosphate (3)-hydroxy (PtdIns(4,5)P2 3-OH) kinase. A similar conclusion has been applied to explain the actions of formyl-Met-Leu-Phe on neutrophils, and it may be that receptors that couple through intrinsic tyrosine kinases or through G proteins stimulate the same step in 3-phosphorylated inositol lipid metabolism. The close parallel between these two mechanisms for the activation of PtdIns(4,5)P2 3-OH kinase and those described for the activation of another key signalling enzyme, phospholipase C (ref. 7), focuses attention on the product of the PtdIns(4,5)P2 3-OH kinase, PtdIns(3,4,5)P3, as a possible new second messenger.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Line
  • Enzyme Activation
  • N-Formylmethionine Leucyl-Phenylalanine / pharmacology
  • Phosphates / metabolism
  • Phosphatidylinositol Phosphates*
  • Phosphatidylinositols / biosynthesis*
  • Phosphorylation
  • Phosphotransferases (Alcohol Group Acceptor)*
  • Phosphotransferases / metabolism*
  • Platelet-Derived Growth Factor / pharmacology*
  • Signal Transduction


  • Phosphates
  • Phosphatidylinositol Phosphates
  • Phosphatidylinositols
  • Platelet-Derived Growth Factor
  • phosphatidylinositol 3,4,5-triphosphate
  • N-Formylmethionine Leucyl-Phenylalanine
  • Phosphotransferases
  • Phosphotransferases (Alcohol Group Acceptor)
  • phosphatidylinositol 4,5-biphosphate kinase