Cross-talk between phospholipase C and phosphoinositide 3-kinase signalling pathways

Biochem Soc Trans. 1997 Nov;25(4):1132-7. doi: 10.1042/bst0251132.

Abstract

1321N1 astrocytoma cells have proved a valuable model system in which to study interactions between two major PtdIns (4,5) P2-utilizing signaling pathways, since they possess receptor populations which elicit independent activation of PI 3-kinase and a G-protein-dependent PLC respectively. Activation of PLC down-regulates PI 3-kinase by at least two mechanisms involving inhibition of IRS-1-associated PI 3-kinase and acute activation of a PtdIns (3,4,5) P3 5-phosphatase. PKB, which is an important early PI 3-kinase-dependent component of insulin signalling pathways, is also down-regulated by PLC-coupled agonists. The activation of PKB by insulin appears to involve a novel PtdIns (3,4,5) P3-dependent protein kinase, which we have named PDK1. The molecular mechanisms underlying PtdIns (3,4,5) P3-stimulated phosphorylation and activation of PKB by PDK1 are currently under investigation.

Publication types

  • Review

MeSH terms

  • Animals
  • Astrocytoma
  • GTP-Binding Proteins / metabolism
  • Insulin / physiology
  • Insulin Receptor Substrate Proteins
  • Phosphatidylinositol 3-Kinases / metabolism*
  • Phosphatidylinositol Phosphates / metabolism*
  • Phosphoproteins / metabolism
  • Signal Transduction*
  • Thrombin / physiology
  • Tumor Cells, Cultured
  • Type C Phospholipases / metabolism*

Substances

  • Insulin
  • Insulin Receptor Substrate Proteins
  • Phosphatidylinositol Phosphates
  • Phosphoproteins
  • Phosphatidylinositol 3-Kinases
  • Type C Phospholipases
  • Thrombin
  • GTP-Binding Proteins