A novel phosphoinositide 3 kinase activity in myeloid-derived cells is activated by G protein beta gamma subunits.
Phosphoinositide 3 kinase (PI3K) is a key signaling enzyme implicated in receptor-stimulated mitogenesis, oxidative bursting in neutrophils, membrane ruffling, and glucose uptake. A PI3K has already been purified, cloned, and shown to be regulated by receptors that act via tyrosine kinase-dependent regulatory mechanisms. We report that an immunologically, pharmacologically, and chromatographically distinct form of PI3K activity present in neutrophils and U937 cells is specifically activated by G protein beta gamma subunits. This data suggests PI3Ks conform to the paradigm set by receptor regulation of phosphoinositidase Cs: different receptor transduction systems specifically regulate dedicated isoforms of effector protein.
Stephens
L
L
Agricultural and Food Research Council, Babraham Institute, Cambridge, England.
Smrcka
A
A
Cooke
F T
FT
Jackson
T R
TR
Sternweis
P C
PC
Hawkins
P T
PT
D000255:Adenosine Triphosphate / Q000378:metabolism; D000730:Androstadienes / Q000494:pharmacology; D000818:Animals; D002417:Cattle; D002460:Cell Line; D004789:Enzyme Activation; D019204:GTP-Binding Proteins / Q000378:metabolism*; D006801:Humans; D007328:Insulin / Q000494:pharmacology; D051379:Mice; D009504:Neutrophils / Q000201:enzymology*; D019869:Phosphatidylinositol 3-Kinases; D010716:Phosphatidylinositols / Q000378:metabolism; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000037:antagonists & inhibitors / Q000378:metabolism*; D015398:Signal Transduction; D013552:Swine; D000077191:Wortmannin
D000730:Androstadienes; D007328:Insulin; D010716:Phosphatidylinositols; D000255:Adenosine Triphosphate; D019869:Phosphatidylinositol 3-Kinases; D017853:Phosphotransferases (Alcohol Group Acceptor); D019204:GTP-Binding Proteins; D000077191:Wortmannin