Phospholipase C-gamma1 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 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-gamma1 (Null cells), and retroviral infection of those cells was used to derive PLC-gamma1 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-gamma1. 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-gamma1. 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-gamma1 is necessary for the maximal expression of many PDGF-induced IEGs and is essential for significant induction of at least five IEGs.
Departments of Biochemistry and Medicine, Vanderbilt University School of Medicine, Nashville, Tennessee 37232-0146, USA.
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HJ
Liao
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Ji
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Carpenter
D000818:Animals; D002460:Cell Line; D005786:Gene Expression Regulation / Q000502:physiology*; D017781:Genes, Immediate-Early; D007527:Isoenzymes / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D051966:Phospholipase C gamma; D010982:Platelet-Derived Growth Factor / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology; D014158:Transcription, Genetic / Q000502:physiology*; D010738:Type C Phospholipases / Q000378:metabolism*
D007527:Isoenzymes; D010982:Platelet-Derived Growth Factor; D010738:Type C Phospholipases; D051966:Phospholipase C gamma