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

J 2008

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

KREJČÍ, Pavel; Lisa SALAZAR; Helen GOODRIDGE; Tamara KASHIWADA; Matthew SCHIBLER et al.

Základní údaje

Originální název

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

Autoři

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

Vydání

JOURNAL OF CELL SCIENCE, 2008, 0021-9533

Další údaje

Jazyk

angličtina

Typ výsledku

Článek v odborném periodiku

Obor

Genetika a molekulární biologie

Stát vydavatele

Spojené státy

Utajení

není předmětem státního či obchodního tajemství

Impakt faktor

Impact factor: 6.247

Označené pro přenos do RIV

Ano

Kód RIV

RIV/00216224:14310/08:00067178

Organizační jednotka

Přírodovědecká fakulta

UT WoS

000253425600004

Klíčová slova anglicky

FACTOR RECEPTOR-3 FGFR3; THANATOPHORIC DYSPLASIA; SERINE PHOSPHORYLATION; INHIBITS PROLIFERATION; INTERFERON-GAMMA; PC12 CELLS; ACTIVATION; INDUCTION; KINASE; APOPTOSIS

Změněno: 29. 4. 2014 09:44, prof. Ing. Petr Dvořák, CSc.

Anotace

V originále

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.

Návaznosti

MSM0021622430, záměr

Název: Funkční a molekulární charakteristiky nádorových a normálních kmenových buněk - identifikace cílů pro nová terapeutika a terapeutické strategie

Investor: Ministerstvo školství, mládeže a tělovýchovy ČR, Funkční a molekulární charakteristiky nádorových a normálních kmenových buněk - identifikace cílů pro nová terapeutika a terapeutické strategie

Citovat

KREJČÍ, Pavel; Lisa SALAZAR; Helen GOODRIDGE; Tamara KASHIWADA; Matthew SCHIBLER; Petra JELÍNKOVÁ; Leslie Michels THOMPSON, a William WILCOX. STAT1 and STAT3 do not participate in FGF-mediated growth arrest in chondrocytes. JOURNAL OF CELL SCIENCE. 2008, roč. 121, č. 3, s. 272-81, 11 s. ISSN 0021-9533.

@article{879430,
   author = {Krejčí, Pavel and Salazar, Lisa and Goodridge, Helen and Kashiwada, Tamara and Schibler, Matthew and Jelínková, Petra and Thompson,, Leslie Michels and Wilcox, William},
   article_number = {3},
   keywords = {FACTOR RECEPTOR-3 FGFR3; THANATOPHORIC DYSPLASIA; SERINE PHOSPHORYLATION; INHIBITS PROLIFERATION; INTERFERON-GAMMA; PC12 CELLS; ACTIVATION; INDUCTION; KINASE; APOPTOSIS},
   language = {eng},
   issn = {0021-9533},
   journal = {JOURNAL OF CELL SCIENCE},
   title = {STAT1 and STAT3 do not participate in FGF-mediated growth arrest in chondrocytes},
   volume = {121},
   year = {2008}
}

TY  - JOUR
ID  - 879430
AU  - Krejčí, Pavel - Salazar, Lisa - Goodridge, Helen - Kashiwada, Tamara - Schibler, Matthew - Jelínková, Petra - Thompson,, Leslie Michels - Wilcox, William
PY  - 2008
TI  - STAT1 and STAT3 do not participate in FGF-mediated growth arrest in chondrocytes
JF  - JOURNAL OF CELL SCIENCE
VL  - 121
IS  - 3
SP  - 272-81
EP  - 272-81
SN  - 00219533
KW  - FACTOR RECEPTOR-3 FGFR3
KW  - THANATOPHORIC DYSPLASIA
KW  - SERINE PHOSPHORYLATION
KW  - INHIBITS PROLIFERATION
KW  - INTERFERON-GAMMA
KW  - PC12 CELLS
KW  - ACTIVATION
KW  - INDUCTION
KW  - KINASE
KW  - APOPTOSIS
N2  - 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.
ER  -

KREJČÍ, Pavel; Lisa SALAZAR; Helen GOODRIDGE; Tamara KASHIWADA; Matthew SCHIBLER; Petra JELÍNKOVÁ; Leslie Michels THOMPSON, a William WILCOX. STAT1 and STAT3 do not participate in FGF-mediated growth arrest in chondrocytes. \textit{JOURNAL OF CELL SCIENCE}. 2008, roč.~121, č.~3, s.~272-81, 11 s. ISSN~0021-9533.

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