STAT1 and STAT3 do not participate in FGF-mediated growth arrest in chondrocytes
| Authors | |
|---|---|
| Year of publication | 2008 |
| Type | Article in Periodical |
| Magazine / Source | JOURNAL OF CELL SCIENCE |
| MU Faculty or unit | |
| Citation | |
| Field | Genetics and molecular biology |
| Keywords | FACTOR RECEPTOR-3 FGFR3; THANATOPHORIC DYSPLASIA; SERINE PHOSPHORYLATION; INHIBITS PROLIFERATION; INTERFERON-GAMMA; PC12 CELLS; ACTIVATION; INDUCTION; KINASE; APOPTOSIS |
| Description | 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. |
| Related projects: |