STAT1 and STAT3 do not participate in FGF-mediated growth arrest in chondrocytes

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Publikace nespadá pod Lékařskou fakultu, ale pod Přírodovědeckou fakultu. Oficiální stránka publikace je na webu muni.cz.

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KREJČÍ Pavel SALAZAR Lisa GOODRIDGE Helen KASHIWADA Tamara SCHIBLER Matthew JELÍNKOVÁ Petra THOMPSON, Leslie Michels WILCOX William

Rok publikování 2008
Druh Článek v odborném periodiku
Časopis / Zdroj JOURNAL OF CELL SCIENCE
Fakulta / Pracoviště MU

Přírodovědecká fakulta

Citace
Obor Genetika a molekulární biologie
Klíčová slova FACTOR RECEPTOR-3 FGFR3; THANATOPHORIC DYSPLASIA; SERINE PHOSPHORYLATION; INHIBITS PROLIFERATION; INTERFERON-GAMMA; PC12 CELLS; ACTIVATION; INDUCTION; KINASE; APOPTOSIS
Popis 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.
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