Platelet-derived growth factor (PDGF) stimulates phospholipase C (PLC) activity and the phosphorylation of the γ isozyme of PLC (PLC-γ) in vitro and in living cells. The role of PLC-γ in the phosphoinositide signaling pathway was addressed by examining the effect of overexpression of PLC-γ on cellular responses to PDGF. Overexpression of PLC-γ correlated with PDGF-induced tyrosine phosphorylation of PLC-γ 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-γ 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.
|Number of pages||4|
|State||Published - 4 May 1990|