Bisindolylmaleimide I suppresses fibroblast growth
factor-mediated activation of  Erk MAP kinase in chondrocytes
by preventing Shp2 association with the Frs2 and Gab1 adaptor
proteins.

J 2006

Bisindolylmaleimide I suppresses fibroblast growth factor-mediated activation of Erk MAP kinase in chondrocytes by preventing Shp2 association with the Frs2 and Gab1 adaptor proteins.

KREJČÍ, Pavel; B. MASRI; L. SALAZAR; C. FARRINGTON-ROCK; H. PRATS et al.

Základní údaje

Originální název

Bisindolylmaleimide I suppresses fibroblast growth factor-mediated activation of Erk MAP kinase in chondrocytes by preventing Shp2 association with the Frs2 and Gab1 adaptor proteins.

Název česky

Bisindolylmaleimide I suppresses fibroblast growth factor-mediated activation of Erk MAP kinase in chondrocytes by preventing Shp2 association with the Frs2 and Gab1 adaptor proteins.

Autoři

KREJČÍ, Pavel; B. MASRI; L. SALAZAR; C. FARRINGTON-ROCK; H. PRATS; L.M. THOMPSON a W.R. WILCOX

Vydání

Journal of Biological Chemistry, Bethesda, USA, Amer. Soc. Biochem. Mol. 2006, 0021-9258

Další údaje

Jazyk

angličtina

Typ výsledku

Článek v odborném periodiku

Obor

30105 Physiology

Stát vydavatele

Spojené státy

Utajení

není předmětem státního či obchodního tajemství

Odkazy

URL

Impakt faktor

Impact factor: 5.808

Označené pro přenos do RIV

Ano

Organizační jednotka

Přírodovědecká fakulta

DOI

https://doi.org/10.1074/jbc.M606144200

UT WoS

000243793900019

Klíčová slova anglicky

TYROSINE KINASE; PC12 CELLS; TRANSCRIPTIONAL ACTIVATION; POTENT INHIBITORS; ENDOTHELIAL-CELLS; FGF RECEPTORS

Změněno: 20. 3. 2012 14:22, Mgr. Jiřina Medalová, Ph.D.

Anotace

V originále

Fibroblast growth factors (FGFs) inhibit chondrocyte proliferation via the Erk MAP kinase pathway. Here, we explored the role of protein kinase C in FGF signaling in chondrocytes. Erk activity in FGF2-treated RCS (rat chondrosarcoma) chondrocytes or human primary chondrocytes was abolished by the protein kinase C inhibitor bisindolylmaleimide I (Bis I). Bis I inhibited FGF2-induced activation of MEK, Raf-1, and Ras members of Erk signaling module but not the FGF2-induced tyrosine phosphorylation of Frs2 or the kinase activity of FGFR3, demonstrating that it targets the Erk cascade immediately upstream of Ras. Indeed, Bis I abolished the FGF2-mediated association of Shp2 tyrosine phosphatase with Frs2 and Gab1 adaptor proteins necessary for proper Ras activation. We also determined which PKC isoform is involved in FGF2-mediated activation of Erk. When both conventional and novel PKCs expressed by RCS chondrocytes ( PKC alpha, -gamma, -delta, and -is an element of) were down-regulated by phorbol ester, cells remained responsive to FGF2 with Erk activation, and this activation was sensitive to Bis I. Moreover, treatment with PKC lambda/xi pseudosubstrate lead to significant reduction of FGF2-mediated activation of Erk, suggesting involvement of an atypical PKC.

Návaznosti

MSM0021622415, záměr

Název: Molekulární podstata buněčných a tkáňových regulací

Investor: Ministerstvo školství, mládeže a tělovýchovy ČR, Molekulární podstata buněčných a tkáňových regulací

Citovat

KREJČÍ, Pavel; B. MASRI; L. SALAZAR; C. FARRINGTON-ROCK; H. PRATS; L.M. THOMPSON a W.R. WILCOX. Bisindolylmaleimide I suppresses fibroblast growth factor-mediated activation of Erk MAP kinase in chondrocytes by preventing Shp2 association with the Frs2 and Gab1 adaptor proteins. Journal of Biological Chemistry. Bethesda, USA: Amer. Soc. Biochem. Mol., 2006, roč. 282, č. 5, s. 2929-2936. ISSN 0021-9258. Dostupné z: https://doi.org/10.1074/jbc.M606144200.

@article{971677,
   author = {Krejčí, Pavel and Masri, B. and Salazar, L. and FarringtonandRock, C. and Prats, H. and Thompson, L.M. and Wilcox, W.R.},
   article_location = {Bethesda, USA},
   article_number = {5},
   doi = {https://doi.org/10.1074/jbc.M606144200},
   keywords = {TYROSINE KINASE; PC12 CELLS; TRANSCRIPTIONAL ACTIVATION; POTENT INHIBITORS; ENDOTHELIAL-CELLS; FGF RECEPTORS},
   language = {eng},
   issn = {0021-9258},
   journal = {Journal of Biological Chemistry},
   title = {Bisindolylmaleimide I suppresses fibroblast growth factor-mediated activation of Erk MAP kinase in chondrocytes by preventing Shp2 association with the Frs2 and Gab1 adaptor proteins.},
   url = {http://dx.doi.org/10.1074/jbc.M606144200},
   volume = {282},
   year = {2006}
}

TY  - JOUR
ID  - 971677
AU  - Krejčí, Pavel - Masri, B. - Salazar, L. - Farrington-Rock, C. - Prats, H. - Thompson, L.M. - Wilcox, W.R.
PY  - 2006
TI  - Bisindolylmaleimide I suppresses fibroblast growth factor-mediated activation of Erk MAP kinase in chondrocytes by preventing Shp2 association with the Frs2 and Gab1 adaptor proteins.
JF  - Journal of Biological Chemistry
VL  - 282
IS  - 5
SP  - 2929-2936
EP  - 2929-2936
PB  - Amer. Soc. Biochem. Mol.
SN  - 00219258
KW  - TYROSINE KINASE
KW  - PC12 CELLS
KW  - TRANSCRIPTIONAL ACTIVATION
KW  - POTENT INHIBITORS
KW  - ENDOTHELIAL-CELLS
KW  - FGF RECEPTORS
UR  - http://dx.doi.org/10.1074/jbc.M606144200
L2  - http://dx.doi.org/10.1074/jbc.M606144200
N2  - Fibroblast growth factors (FGFs) inhibit chondrocyte proliferation via the Erk MAP kinase pathway. Here, we explored the role of protein kinase C in FGF signaling in chondrocytes. Erk activity in FGF2-treated RCS (rat chondrosarcoma) chondrocytes or human primary chondrocytes was abolished by the protein kinase C inhibitor bisindolylmaleimide I (Bis I). Bis I inhibited FGF2-induced activation of MEK, Raf-1, and Ras members of Erk signaling module but not the FGF2-induced tyrosine phosphorylation of Frs2 or the kinase activity of FGFR3, demonstrating that it targets the Erk cascade immediately upstream of Ras. Indeed, Bis I abolished the FGF2-mediated association of Shp2 tyrosine phosphatase with Frs2 and Gab1 adaptor proteins necessary for proper Ras activation. We also determined which PKC isoform is involved in FGF2-mediated activation of Erk. When both conventional and novel PKCs expressed by RCS chondrocytes ( PKC alpha, -gamma, -delta, and -is an element of) were down-regulated by phorbol ester, cells remained responsive to FGF2 with Erk activation, and this activation was sensitive to Bis I. Moreover, treatment with PKC lambda/xi pseudosubstrate lead to significant reduction of FGF2-mediated activation of Erk, suggesting involvement of an atypical PKC.
ER  -

KREJČÍ, Pavel; B. MASRI; L. SALAZAR; C. FARRINGTON-ROCK; H. PRATS; L.M. THOMPSON a W.R. WILCOX. Bisindolylmaleimide I suppresses fibroblast growth factor-mediated activation of Erk MAP kinase in chondrocytes by preventing Shp2 association with the Frs2 and Gab1 adaptor proteins. \textit{Journal of Biological Chemistry}. Bethesda, USA: Amer. Soc. Biochem. Mol., 2006, roč.~282, č.~5, s.~2929-2936. ISSN~0021-9258. Dostupné z: https://doi.org/10.1074/jbc.M606144200.

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