PMID- 15213220
OWN - NLM
STAT- MEDLINE
DCOM- 20050215
LR  - 20210206
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 279
IP  - 34
DP  - 2004 Aug 20
TI  - Platelet-derived growth factor stimulates membrane lipid synthesis through 
      activation of phosphatidylinositol 3-kinase and sterol regulatory element-binding 
      proteins.
PG  - 35392-402
AB  - We analyzed the transcriptional program elicited by stimulation of normal human 
      fibroblasts with platelet-derived growth factor (PDGF) using cDNA microarrays. 
      103 significantly regulated transcripts that had not been previously linked to 
      PDGF signaling were identified. Among them, a cluster of genes involved in fatty 
      acid and cholesterol biosynthesis, including stearoyl-CoA desaturase (SCD), fatty 
      acid synthase, and hydroxymethylglutaryl-CoA synthase (HMGCS), was up-regulated 
      by PDGF after 24 h of treatment, and their expression correlated with increased 
      membrane lipid production. These genes are known to be controlled by sterol 
      regulatory element-binding proteins (SREBP). PDGF increased the amount of mature 
      SREBP-1 and regulated the promoters of SCD and HMGCS in an SREBP-dependent 
      manner. In line with these results, blocking SREBP processing by addition of 
      25-hydroxycholesterol blunted the effects of PDGF on lipogenic enzymes. SREBP 
      activation was dependent on the phosphatidylinositol 3-kinase (PI3K) pathway, as 
      judged from the effects of the inhibitor LY294002 and mutation of the PDGFbeta 
      receptor tyrosines that bind the PI3K adaptor subunit p85. Fibroblast growth 
      factors (FGF-2 and FGF-4) and other growth factors mimicked the effects of PDGF 
      on NIH3T3 and human fibroblasts. In conclusion, our results suggest that growth 
      factors induce membrane lipid synthesis via the activation SREBP and PI3K.
FAU - Demoulin, Jean-Baptiste
AU  - Demoulin JB
AD  - Ludwig Institute for Cancer Research, Uppsala Branch, Biomedical Centre, Box 595, 
      SE-75124 Uppsala, Sweden. jean-baptiste.demoulin@mexp.ucl.ac.be
FAU - Ericsson, Johan
AU  - Ericsson J
FAU - Kallin, Anders
AU  - Kallin A
FAU - Rorsman, Charlotte
AU  - Rorsman C
FAU - Ronnstrand, Lars
AU  - Ronnstrand L
FAU - Heldin, Carl-Henrik
AU  - Heldin CH
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20040622
PL  - United States
TA  - J Biol Chem
JT  - The Journal of biological chemistry
JID - 2985121R
RN  - 0 (CCAAT-Enhancer-Binding Proteins)
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (Membrane Lipids)
RN  - 0 (SREBF1 protein, human)
RN  - 0 (Sterol Regulatory Element Binding Protein 1)
RN  - 0 (Transcription Factors)
RN  - EC 2.7.1.- (Phosphatidylinositol 3-Kinases)
SB  - IM
MH  - CCAAT-Enhancer-Binding Proteins/*metabolism
MH  - Cells, Cultured
MH  - DNA-Binding Proteins/*metabolism
MH  - Enzyme Activation/drug effects
MH  - Gene Expression Regulation/*drug effects
MH  - Humans
MH  - Membrane Lipids/*biosynthesis/*genetics
MH  - Phosphatidylinositol 3-Kinases/*metabolism
MH  - Sterol Regulatory Element Binding Protein 1
MH  - Transcription Factors/*metabolism
EDAT- 2004/06/24 05:00
MHDA- 2005/02/16 09:00
CRDT- 2004/06/24 05:00
PHST- 2004/06/24 05:00 [pubmed]
PHST- 2005/02/16 09:00 [medline]
PHST- 2004/06/24 05:00 [entrez]
AID - S0021-9258(20)73119-4 [pii]
AID - 10.1074/jbc.M405924200 [doi]
PST - ppublish
SO  - J Biol Chem. 2004 Aug 20;279(34):35392-402. doi: 10.1074/jbc.M405924200. Epub 
      2004 Jun 22.