STAT1 and STAT3 do not participate in FGF-mediated growth arrest in chondrocytes
Language English Country Great Britain, England Media print-electronic
Document type Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't
Grant support
5P01-HD22657
NICHD NIH HHS - United States
PubMed
18198189
DOI
10.1242/jcs.017160
PII: jcs.017160
Knihovny.cz E-resources
- MeSH
- Cell Line MeSH
- Chondrocytes cytology drug effects metabolism MeSH
- Fibroblast Growth Factors metabolism pharmacology MeSH
- Fibroblast Growth Factor 2 metabolism pharmacology MeSH
- Phosphorylation MeSH
- Interferon-gamma pharmacology MeSH
- Interleukin-6 pharmacology MeSH
- Humans MeSH
- Luminescent Proteins genetics metabolism MeSH
- RNA, Small Interfering genetics MeSH
- Mutagenesis, Site-Directed MeSH
- Cell Proliferation drug effects MeSH
- Receptor, Fibroblast Growth Factor, Type 3 genetics metabolism MeSH
- Recombinant Fusion Proteins genetics metabolism MeSH
- Recombinant Proteins MeSH
- RNA Interference MeSH
- Base Sequence MeSH
- Signal Transduction MeSH
- Transfection MeSH
- STAT1 Transcription Factor genetics metabolism MeSH
- STAT3 Transcription Factor antagonists & inhibitors genetics metabolism MeSH
- Green Fluorescent Proteins genetics metabolism MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Research Support, N.I.H., Extramural MeSH
- Names of Substances
- FGFR3 protein, human MeSH Browser
- Fibroblast Growth Factors MeSH
- Fibroblast Growth Factor 2 MeSH
- Interferon-gamma MeSH
- Interleukin-6 MeSH
- Luminescent Proteins MeSH
- RNA, Small Interfering MeSH
- Receptor, Fibroblast Growth Factor, Type 3 MeSH
- Recombinant Fusion Proteins MeSH
- Recombinant Proteins MeSH
- STAT1 protein, human MeSH Browser
- STAT3 protein, human MeSH Browser
- STAT1 Transcription Factor MeSH
- STAT3 Transcription Factor MeSH
- Green Fluorescent Proteins MeSH
Activating mutations in fibroblast growth factor receptor 3 (FGFR3) cause several human skeletal dysplasias as a result of attenuation of cartilage growth. It is believed that FGFR3 inhibits chondrocyte proliferation via activation of signal transducers and activators of transcription (STAT) proteins, although the exact mechanism of both STAT activation and STAT-mediated inhibition of chondrocyte growth is unclear. We show that FGFR3 interacts with STAT1 in cells and is capable of activating phosphorylation of STAT1 in a kinase assay, thus potentially serving as a STAT1 kinase in chondrocytes. However, as demonstrated by western blotting with phosphorylation-specific antibodies, imaging of STAT nuclear translocation, STAT transcription factor assays and STAT luciferase reporter assays, FGF does not activate STAT1 or STAT3 in RCS chondrocytes, which nevertheless respond to a FGF stimulus with potent growth arrest. Moreover, addition of active STAT1 and STAT3 to the FGF signal, by means of cytokine treatment, SRC-mediated STAT activation or expression of constitutively active STAT mutants does not sensitize RCS chondrocytes to FGF-mediated growth arrest. Since FGF-mediated growth arrest is rescued by siRNA-mediated downregulation of the MAP kinase ERK1/2 but not STAT1 or STAT3, our data support a model whereby the ERK arm but not STAT arm of FGF signaling in chondrocytes accounts for the growth arrest phenotype.
References provided by Crossref.org
Increased thermal stability of FGF10 leads to ectopic signaling during development
Instability restricts signaling of multiple fibroblast growth factors