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Papers In Press, published online ahead of print January 30, 2001
J. Biol. Chem, 10.1074/jbc.C100030200
Submitted on January 19, 2001
Revised on January 30, 2001
Accepted on January 30, 2001
1 is required for the induction of immediate early genes by platelet-derived growth factor
Department of Biochemistry, Vanderbilt University School of Medicine, Nashville, TN 37232-0146
Corresponding Author: graham.carpenter{at}mcmail.vanderbilt.edu
To explore the functional role of phospholipase C-
1 (PLC-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-1 (Null cells) and retroviral infection of those cells was used to derive PLC-1 re-expressing cells (Null+ cells). In terms of PDGF activation of PDGF receptor tyrosine phosphorylation as well as the mitogen-activated protein kinases Erk-1 and Erk-2, Null and Null+ cells responded equivalently. However, the PDGF-dependent expression of all IEG mRNAs was diminished in cells lacking PLC-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-1. The combination of PMA and ionomycin, downstream analogues of PLC activation, did provoke expression of mRNAs for these IEGs in the Null cells. We conclude that PLC-1 is necessary for the maximal expression of many PDGF-induced IEGs and is essential for significant induction of at least five IEGs.
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