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Originally published In Press as doi:10.1074/jbc.C100030200 on January 30, 2001

J. Biol. Chem., Vol. 276, Issue 12, 8627-8630, March 23, 2001
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ACCELERATED PUBLICATION
Phospholipase C-gamma 1 Is Required for the Induction of Immediate Early Genes by Platelet-derived Growth Factor*

Hong-Jun LiaoDagger , Qun-Sheng JiDagger §, and Graham CarpenterDagger ||

From the Departments of Dagger  Biochemistry and  Medicine, Vanderbilt University School of Medicine, Nashville, Tennessee 37232-0146

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.

* This work was supported by Grant CA75195 from the National Institutes of Health.The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

§ Present address: Onyx Pharmaceuticals Inc., Richmond, CA 94806.

|| To whom correspondence should be addressed. Tel.: 615-322-6678; Fax: 615-322-2931; E-mail: graham.carpenter@mcmail.vanderbilt.edu.

Copyright © 2001 by The American Society for Biochemistry and Molecular Biology, Inc.


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