Margolis B, Zilberstein A, Franks C, Felder S, Kremer S, Ullrich A, Rhee S G, Skorecki K, Schlessinger J
Rorer Biotechnology, King of Prussia, PA 19406.
Science. 1990 May 4;248(4955):607-10. doi: 10.1126/science.2333512.
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.
血小板衍生生长因子（PDGF）在体外和活细胞中均可刺激磷脂酶C（PLC）的活性以及PLC的γ同工酶（PLC-γ）的磷酸化。通过检测PLC-γ过表达对细胞对PDGF反应的影响，探讨了PLC-γ在磷酸肌醇信号通路中的作用。PLC-γ的过表达与PDGF诱导的PLC-γ酪氨酸磷酸化以及PDGF诱导的磷脂酰肌醇4,5-二磷酸（PIP2）的分解相关。然而，转染细胞中缓激肽或溶血磷脂酸诱导的磷酸肌醇代谢均未增强，这表明对这些配体的G蛋白偶联磷酸肌醇反应是由其他PLC同工酶介导的。PDGF诱导的肌醇三磷酸（IP3）生成增强并未增强细胞内钙信号传导，也未影响PDGF诱导的DNA合成。因此，除PLC-γ以外的酶可能会限制PDGF诱导的钙信号传导和DNA合成。或者，PDGF诱导的钙信号传导和DNA合成可能使用磷酸肌醇代谢以外的生化途径进行信号转导。
