Phospholipase C- gamma 1 Is Required for the Induction of Immediate Early Genes by Platelet-derived Growth Factor

• Published in: The Journal of biological chemistry 2001-03, Vol.276 (12), p.8627-8630
• Main Authors: Liao, HJ, Ji, Q S, Carpenter, G
• Format: Article
• Language: English
• Subjects: c-fos gene; COX-2 gene; Erk1 protein; Erk2 protein; FIC gene; immediate early gene; JE gene; KC gene; Plcg1 gene
• ISSN: 0021-9258
• DOI: 10.1074/jbc.C100030200

To explore the functional role of phospholipase C- gamma 1 (PLC- gamma 1) in the induction of immediate early genes (IEGs), we have examined the influence of Plcg1 gene disruption on the expression of 14 IEG mRNAs induced by platelet-derived growth factor (PDGF). Plcg1-null embryos were used to produce immortalized fibroblasts genetically deficient in PLC- gamma 1 (Null cells), and retroviral infection of those cells was used to derive PLC- gamma 1 re-expressing cells (Null+ cells). In terms of PDGF activation of PDGF receptor tyrosine phosphorylation as well as the mitogen-activated protein kinases Erk1 and Erk2, Null and Null+ cells responded equivalently. However, the PDGF-dependent expression of all IEG mRNAs was diminished in cells lacking PLC- gamma 1. The expression of FIC, COX-2, KC, JE, and c-fos mRNAs were most strongly compromised, as the stimulation of these genes was reduced by more than 90% in cells lacking PLC- gamma 1. The combination of PMA and ionomycin, downstream analogs of PLC activation, did provoke expression of mRNAs for these IEGs in the Null cells. We conclude that PLC- gamma 1 is necessary for the maximal expression of many PDGF- induced IEGs and is essential for significant induction of at least five IEGs.