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 (203 Česká republika, garant, domácí), Lisa SALAZAR (840 Spojené státy), Helen GOODRIDGE (840 Spojené státy), Tamara KASHIWADA (840 Spojené státy), Matthew SCHIBLER (840 Spojené státy), Petra JELÍNKOVÁ (203 Česká republika), Leslie Michels THOMPSON, (840 Spojené státy) a William WILCOX (840 Spojené státy)

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

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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