Effect of phospholipase C-gamma overexpression on PDGF-induced second messengers and mitogenesis.
Platelet-derived growth factor (PDGF) stimulates phospholipase C (PLC) activity and the phosphorylation of the gamma isozyme of PLC (PLC-gamma) in vitro and in living cells. The role of PLC-gamma in the phosphoinositide signaling pathway was addressed by examining the effect of overexpression of PLC-gamma on cellular responses to PDGF. Overexpression of PLC-gamma correlated with PDGF-induced tyrosine phosphorylation of PLC-gamma and with PDGF-induced breakdown of phosphatidylinositol 4,5-bisphosphate (PIP2). However, neither bradykinin- nor lysophosphatidic acid-induced phosphoinositide metabolism was enhanced in the transfected cells, suggesting that the G protein-coupled phosphoinositide responses to these ligands are mediated by other PLC isozymes. The enhanced PDGF-induced generation of inositol trisphosphate (IP3) did not enhance intracellular calcium signaling or influence PDGF-induced DNA synthesis. Thus, enzymes other than PLC-gamma may limit PDGF-induced calcium signaling and DNA synthesis. Alternatively, PDGF-induced calcium signaling and DNA synthesis may use biochemical pathways other than phosphoinositide metabolism for signal transduction.
Margolis
B
B
Rorer Biotechnology, King of Prussia, PA 19406.
Zilberstein
A
A
Franks
C
C
Felder
S
S
Kremer
S
S
Ullrich
A
A
Rhee
S G
SG
Skorecki
K
K
Schlessinger
J
J
D000818:Animals; D002118:Calcium / Q000502:physiology; D002417:Cattle; D002455:Cell Division / Q000187:drug effects*; D002478:Cells, Cultured; D004261:DNA Replication / Q000187:drug effects; D005822:Genetic Vectors; D007295:Inositol Phosphates / Q000378:metabolism; D007527:Isoenzymes / Q000096:biosynthesis / Q000235:genetics* / Q000378:metabolism; D007700:Kinetics; D051379:Mice; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology*; D015290:Second Messenger Systems / Q000187:drug effects*; D014162:Transfection; D010738:Type C Phospholipases / Q000096:biosynthesis / Q000235:genetics* / Q000378:metabolism
D007295:Inositol Phosphates; D007527:Isoenzymes; D010982:Platelet-Derived Growth Factor; D010738:Type C Phospholipases; D002118:Calcium