Phospholipase C-gamma 1 is required for the induction of immediate early genes by platelet-derived growth factor

To explore the functional role of phospholipase C-gamma1 (PLC-gamma1) in th e induction of immediate early genes (IEGs), we have examined the influence of PLcg1 gene disruption on the expression of 14 IEG mRNAs induced by plat elet-derived growth factor (PDGF). Plcg1-null embryos were used to produce immortalized fibroblasts genetically deficient in PLC-gamma1 (Null cells), and retroviral infection of those cells was used to derive PLC-gamma1 re-ex pressing cells (Null+ cells). In terms of PDGF activation of PDGF receptor tyrosine phosphorylation as well as the mitogen-activated protein kinases E rk1 and Erk2, Null and Null+ cells responded equivalently. However, the PDG F-dependent expression of all IEG mRNAs was diminished in cells lacking PLC -gamma1. The expression of FIC, COX-2, KC, JE, and c-fos mRNAs were most st rongly compromised, as the stimulation of these genes was reduced by more t han 90% in cells lacking PLC-gamma1, The combination of PIMA and ionomycin, downstream analogs of PLC activation, did provoke expression of mRNAs for these IEGs in the Null cells. We conclude that PLC-gamma1 is necessary for the maximal expression of many PDGF-induced IEGs and is essential for signi ficant induction of at least five IEGs.