Over‐expression of human phospholipase C‐γ2 enhances platelet‐derived growth factor‐induced mobilization of intracellular Ca2+ and the release of arachidonic acid and prostaglandins in NIH 3T3 fibroblasts

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Abstract
Over-expression of human phospholipase C-γ2 in murine NIH 3T3 fibroblasis has been shown to result in an increased platelet-derived growth factor-mediated formation of inositol phosphates. Here we show that phospholipase C-γ2 over-expression is associated with an increased platelet-derived growth factor-mediated release of arachidonic acid, prostaglandin E2, 6-keto prostaglandin F10 and prostaglandin F20. The phorbol ester, calcium ionophore- and fluoride-induced release of arachidonate and its metabolites is not affected by phospholipase C-γ2 over-expression. Over-expression of phospholipase C-γ2 is also associated with an enhancement of platelet-derived growth factor-induced change in intracellular Ca2+. These results demonstrate that stimulation of recombinant human phospholipase C-γ2 induces a change in the intracellular Ca2+ concentration, a release of arachidonic acid and formation of prostaglandins in NIH 3T3 cells. In control cells platelet-derived growth factor-induced activation of arachidonic acid cascade is rate-limited by the endogenous phospholipase C.