The Role Of Phospholipase C-gammal In Cells Mitogenic Signal Transduction Induced By Platelet-derived Growth Factor

In mammalian cells there are approximately ten phospholipase(PLC) enzymes, including PLC- f3 PLC- γ and PLC- γ , which mediate the hydrolysis of phosphatidylinositol 4,5-dipho phatc(PIP2) to the second messenger molecules inositol l,4,5-.triphosphate(1P3) and diaclglycetol. ( DAG). PLC- γ is the only PLC- γ isoform which has SF12 and S113 domain, and is activated by several growth factor tyrosine kinase receptors, for example epiderinal growth factor(EGF), fibroblast rowth factor(FGF), platelet-derived growth factor(PDGF) and netve growth fact or(NGF). Following the activation of receptor kinase by ligand binding, PLC- v I associates with activated receptors, and in turn is phosphorylated on tyrosine residues by these receptor tyrosine kinase. The activated PLC-γ 1 then translocaies to the membrane, and causes the hydrolysis of PIP2 to 1P3 and DAG. But what the role of PLC-γ 1 in growth factor Hduced cells mitogenic signal transduction is not clear. Object: To assess the role of PLC- γ 1 in PDGF induced cells niitogenic signal transduction. Methods: Using the immortalized fibroblasts genetically deficient in PLC-γ 1 ,(1) To study Ihe concequence of absence of PLC- γ 1 on cells growth: making cells growth curve and cells colony fonnation were observed. (2) To itstigate cells shape and constructure by electron microscope. (3) To assess the role of PLC- γ 1 in PDGF induced ce~ Is migration. (4) Using 3j TdR to reseach the role of PLC- γ 1 in PDGF induced DNA syndiesis. (5) To assess role of PLC- γ 1 in mobilization of intracellular Results: (1) On cells growth.. colony formation.. constructure.. cells migration.. DNA synthesis and intracellular Ca4+ mobilization , absence of PDGF, cells deficient in PLC- γ 1(PLC-γ 1) equal to normal cells(PLC-γ 1). (2) Stimulated with PDGF, both PLC- γ 1 and PLC- v 1 cells represent of multiplication, the latter is more bloom. And both DNA synthesis is increased.. intrcellular Ca~4+ mobilization is appeared. But in PLC-γ 1 cells, the time of DNA synthesis were prolonged, and the mobilization of Ca~4+ were attenuated and postpone. Conclusion: 1. PLC-γ 1 is important in cells rnitogenic signal transduction induced by PDGF. 2. Deficient in PLC- γ I, the effect of PLC- γ I could be substituted by other signal molecule. 3 PDGF?is important in regulation of cells mitogenic through PLC-γ 1.