Cross-talk between phospholipase C and phosphoinositide 3-kinase signalling pathways.
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.
Batty
I H
IH
Department of Biochemistry, University of Dundee, U.K.
Hickinson
D M
DM
Downes
C P
CP
D000818:Animals; D001254:Astrocytoma; D019204:GTP-Binding Proteins / Q000378:metabolism; D007328:Insulin / Q000502:physiology; D055504:Insulin Receptor Substrate Proteins; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D018129:Phosphatidylinositol Phosphates / Q000378:metabolism*; D010750:Phosphoproteins / Q000378:metabolism; D015398:Signal Transduction; D013917:Thrombin / Q000502:physiology; D014407:Tumor Cells, Cultured; D010738:Type C Phospholipases / Q000378:metabolism*
D007328:Insulin; D055504:Insulin Receptor Substrate Proteins; D018129:Phosphatidylinositol Phosphates; D010750:Phosphoproteins; D019869:Phosphatidylinositol 3-Kinases; D010738:Type C Phospholipases; D013917:Thrombin; D019204:GTP-Binding Proteins