Increase of the catalytic activity of phospholipase C-gamma 1 by tyrosine phosphorylation.
Phospholipase C-gamma 1 (PLC-gamma 1), an isozyme of the phosphoinositide-specific phospholipase C family, which occupies a central role in hormonal signal transduction pathways, is an excellent substrate for the epidermal growth factor (EGF) receptor tyrosine kinase. Epidermal growth factor elicits tyrosine phosphorylation of PLC-gamma 1 and phosphatidylinositol 4,5-bisphosphate hydrolysis in various cell lines. The ability of tyrosine phosphorylation to activate the catalytic activity of PLC-gamma 1 was tested. Tyrosine phosphorylation in intact cells or in vitro increased the catalytic activity of PLC-gamma 1. Also, treatment of EGF-activated PLC-gamma 1 with a tyrosine-specific phosphatase substantially decreased the catalytic activity of PLC-gamma 1. These results suggest that the EGF-stimulated formation of inositol 1,4,5-trisphosphate and diacylglycerol in intact cells results, at least in part, from catalytic activation of PLC-gamma 1 through tyrosine phosphorylation.
Department of Biochemistry, Vanderbilt University School of Medicine, Nashville, TN 37232-0146.
S
S
Nishibe
M I
MI
Wahl
S M
SM
Hernández-Sotomayor
N K
NK
Tonks
S G
SG
Rhee
G
G
Carpenter
D002384:Catalysis; D004075:Diglycerides / Q000378:metabolism; D004789:Enzyme Activation / Q000187:drug effects; D004815:Epidermal Growth Factor / Q000494:pharmacology; D066246:ErbB Receptors; D007163:Immunosorbent Techniques; D015544:Inositol 1,4,5-Trisphosphate / Q000378:metabolism; D007527:Isoenzymes / Q000378:metabolism*; D007700:Kinetics; D019269:Phosphatidylinositol 4,5-Diphosphate; D043265:Phosphatidylinositol Diacylglycerol-Lyase; D010716:Phosphatidylinositols / Q000378:metabolism; D010727:Phosphoric Diester Hydrolases / Q000378:metabolism*; D010766:Phosphorylation; D019000:Phosphotyrosine; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D015398:Signal Transduction; D014443:Tyrosine / Q000031:analogs & derivatives* / Q000378:metabolism
D004075:Diglycerides; D007527:Isoenzymes; D019269:Phosphatidylinositol 4,5-Diphosphate; D010716:Phosphatidylinositols; D019000:Phosphotyrosine; D014443:Tyrosine; D004815:Epidermal Growth Factor; D015544:Inositol 1,4,5-Trisphosphate; D066246:ErbB Receptors; D011505:Protein-Tyrosine Kinases; D010727:Phosphoric Diester Hydrolases; D043265:Phosphatidylinositol Diacylglycerol-Lyase