PMID- 12020352
OWN - NLM
STAT- MEDLINE
DCOM- 20021017
LR  - 20181113
IS  - 0264-6021 (Print)
IS  - 1470-8728 (Electronic)
IS  - 0264-6021 (Linking)
VI  - 366
IP  - Pt 2
DP  - 2002 Sep 1
TI  - A novel role for farnesyl pyrophosphate synthase in fibroblast growth 
      factor-mediated signal transduction.
PG  - 501-10
AB  - 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.
FAU - Reilly, John F
AU  - Reilly JF
AD  - Department of Cell Biology, The Scripps Research Institute, 10550 N. Torrey Pines 
      Road, La Jolla, CA 92037, USA.
FAU - Martinez, Shawndra D
AU  - Martinez SD
FAU - Mickey, Gregory
AU  - Mickey G
FAU - Maher, Pamela A
AU  - Maher PA
LA  - eng
SI  - GENBANK/AF309598
GR  - GM 51604/GM/NIGMS NIH HHS/United States
GR  - NS 28121/NS/NINDS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - England
TA  - Biochem J
JT  - The Biochemical journal
JID - 2984726R
RN  - 0 (Cell Cycle Proteins)
RN  - 0 (Receptors, Fibroblast Growth Factor)
RN  - 0 (Recombinant Proteins)
RN  - 103107-01-3 (Fibroblast Growth Factor 2)
RN  - 62031-54-3 (Fibroblast Growth Factors)
RN  - EC 2.5.- (Alkyl and Aryl Transferases)
RN  - EC 2.5.1.10 (Geranyltranstransferase)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-raf)
RN  - EC 3.6.5.2 (ras Proteins)
SB  - IM
MH  - 3T3 Cells
MH  - Alkyl and Aryl Transferases/*metabolism
MH  - Animals
MH  - Cell Cycle Proteins/metabolism
MH  - Fibroblast Growth Factor 2/*pharmacology
MH  - Fibroblast Growth Factors/*physiology
MH  - Geranyltranstransferase
MH  - Kinetics
MH  - Mice
MH  - Molecular Sequence Data
MH  - Phosphorylation
MH  - Proto-Oncogene Proteins c-raf/metabolism
MH  - Receptors, Fibroblast Growth Factor/physiology
MH  - Recombinant Proteins/metabolism
MH  - Saccharomyces cerevisiae/genetics
MH  - Signal Transduction/*physiology
MH  - Transfection
MH  - ras Proteins/metabolism
PMC - PMC1222793
EDAT- 2002/05/22 10:00
MHDA- 2002/10/18 04:00
PMCR- 2003/03/01
CRDT- 2002/05/22 10:00
PHST- 2002/05/21 00:00 [accepted]
PHST- 2002/05/16 00:00 [revised]
PHST- 2002/04/08 00:00 [received]
PHST- 2002/05/22 10:00 [pubmed]
PHST- 2002/10/18 04:00 [medline]
PHST- 2002/05/22 10:00 [entrez]
PHST- 2003/03/01 00:00 [pmc-release]
AID - BJ20020560 [pii]
AID - 10.1042/BJ20020560 [doi]
PST - ppublish
SO  - Biochem J. 2002 Sep 1;366(Pt 2):501-10. doi: 10.1042/BJ20020560.