Receptor stimulated accumulation of phosphatidylinositol (3,4,5)-trisphosphate by G-protein mediated pathways in human myeloid derived cells

EMBO J. 1993 Jun;12(6):2265-73.

Abstract

Phosphoinositide 30H-kinase (PI3K) activities are thought to be critical regulatory enzymes in a new intracellular signalling pathway, the activation of which results in the rapid accumulation of a putative signalling molecule, phosphatidylinositol (3,4,5)-trisphosphate [PtdIns(3,4,5) P3]. To date, activation of PI3K has always correlated with its recruitment into complexes containing protein tyrosine kinases (PTK). Here we report that agonists which utilize G-protein mediated transduction pathways can stimulate very rapid and large accumulations of PtdIns(3,4,5)P3 via a novel mechanism, possibly involving direct coupling between the G-protein and a PI3K activity. In addition, some of these agonists also stimulate small increases in PI3K activity in anti-phosphotyrosine and anti-src-type PTK antibody directed immunoprecipitates, indicating activation of PI3K via a 'conventional' PTK mediated mechanism; these pathways however, play only a minor role in the initial, agonist sensitive production of PtdIns(3,4,5)P3 in myeloid derived cells.

Publication types

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

MeSH terms

  • Adenosine Triphosphate / metabolism
  • Bone Marrow / drug effects
  • Bone Marrow / enzymology
  • Bone Marrow / metabolism*
  • Cell Line
  • Cells, Cultured
  • GTP-Binding Proteins / metabolism*
  • Humans
  • N-Formylmethionine Leucyl-Phenylalanine / pharmacology
  • Neutrophils / drug effects
  • Neutrophils / enzymology
  • Neutrophils / metabolism*
  • Phosphatidylinositol 3-Kinases
  • Phosphatidylinositol Phosphates*
  • Phosphatidylinositols / metabolism*
  • Phosphotransferases / metabolism
  • Protein-Tyrosine Kinases / metabolism
  • Signal Transduction*

Substances

  • Phosphatidylinositol Phosphates
  • Phosphatidylinositols
  • phosphatidylinositol 3,4,5-triphosphate
  • N-Formylmethionine Leucyl-Phenylalanine
  • Adenosine Triphosphate
  • Phosphotransferases
  • Phosphatidylinositol 3-Kinases
  • Protein-Tyrosine Kinases
  • GTP-Binding Proteins