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 (203 Česká republika, garant, domácí), B. MASRI (840 Spojené státy), L. SALAZAR (840 Spojené státy), C. FARRINGTON-ROCK (840 Spojené státy), H. PRATS (840 Spojené státy), L.M. THOMPSON (840 Spojené státy) a W.R. WILCOX (840 Spojené státy)

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

Organizační jednotka

Přírodovědecká fakulta

DOI

http://dx.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://dx.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 = {http://dx.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://dx.doi.org/10.1074/jbc.M606144200.

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