Farnesyl pyrophosphate synthase (FPPS) catalyses the formation of a key cellular intermediate in isoprenoid metabolic pathways. Here we describe a novel role for this enzyme in fibroblast growth factor (FGF)-mediated signalling. We demonstrate the binding of FPPS to FGF receptors (FGFRs) using the yeast two-hybrid assay, pull-down assays and co-immunoprecipitation. The interaction between FPPS and FGFR is regulated by the cellular metabolic state and by treatment with FGF-2. Overexpression of FPPS inhibits FGF-2-induced cell proliferation, accompanied by a failure of the FGF-2-mediated induction of cyclins D1 and E. Overexpression of FPPS in fibroblasts also promotes increased farnesylation of Ras, and temporally extends FGF-2-stimulated activation of the Ras/ERK (extracellular-signal-regulated kinase) cascade. These data suggest that, in addition to its role in isoprenoid biosynthesis, FPPS may function as a modulator of the cellular response to FGF treatment.
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September 2002
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Research Article|
September 01 2002
A novel role for farnesyl pyrophosphate synthase in fibroblast growth factor-mediated signal transduction
John F. REILLY;
John F. REILLY
1
Department of Cell Biology, The Scripps Research Institute, 10550 N. Torrey Pines Road, La Jolla, CA 92037, U.S.A.
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Shawndra D. MARTINEZ;
Shawndra D. MARTINEZ
Department of Cell Biology, The Scripps Research Institute, 10550 N. Torrey Pines Road, La Jolla, CA 92037, U.S.A.
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Gregory MICKEY;
Gregory MICKEY
Department of Cell Biology, The Scripps Research Institute, 10550 N. Torrey Pines Road, La Jolla, CA 92037, U.S.A.
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Pamela A. MAHER
Pamela A. MAHER
2
Department of Cell Biology, The Scripps Research Institute, 10550 N. Torrey Pines Road, La Jolla, CA 92037, U.S.A.
2To whom correspondence should be addressed (e-mail pmaher@scripps.edu).
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Publisher: Portland Press Ltd
Received:
April 08 2002
Revision Received:
May 16 2002
Accepted:
May 21 2002
Accepted Manuscript online:
May 21 2002
Online ISSN: 1470-8728
Print ISSN: 0264-6021
The Biochemical Society, London ©2002
2002
Biochem J (2002) 366 (2): 501–510.
Article history
Received:
April 08 2002
Revision Received:
May 16 2002
Accepted:
May 21 2002
Accepted Manuscript online:
May 21 2002
Citation
John F. REILLY, Shawndra D. MARTINEZ, Gregory MICKEY, Pamela A. MAHER; A novel role for farnesyl pyrophosphate synthase in fibroblast growth factor-mediated signal transduction. Biochem J 1 September 2002; 366 (2): 501–510. doi: https://doi.org/10.1042/bj20020560
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