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@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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