ID | 111887 |
著者 |
Murakami, Sara
Tokushima University
Komatsu, Hiroaki
Tokushima University
Sawanoi, Masahiro
Tokushima University
Miyamoto, Kenji
Tokushima University
Ishidoh, Kazumi
Tokushima University
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キーワード | PKGII
Raf-1
Chondrocytes
FGF
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資料タイプ |
学術雑誌論文
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抄録 | Although type II cGMP-dependent protein kinase (PKGII) is a major downstream effector of cGMP in chondrocytes and attenuates the FGF receptor 3/ERK signaling pathway, its direct target proteins have not been fully explored. In the present study, we attempted to identify PKGII-targeted proteins, which are associated with the inhibition of FGF-induced MAPK activation. Although FGF2 stimulation induced the phosphorylation of ERK1/2, MEK1/2, and Raf-1 at Ser-338 in rat chondrosarcoma cells, pretreatment with a cell-permeable cGMP analog strongly inhibited their phosphorylation. On the other hand, Ser-43 of Raf-1 was phosphorylated by cGMP in a dose-dependent manner. Therefore, we examined the direct phosphorylation of Raf-1 by PKGII. Wild-type PKGII phosphorylated Raf-1 at Ser-43 in a cGMP-dependent manner, but a PKGII D412A/R415A mutant, which has a low affinity for cGMP, did not. Finally, we found that a phospho-mimic mutant, Raf-1 S43D, suppressed FGF2-induced MAPK pathway. These results suggest that PKGII counters FGF-induced MEK/ERK activation through the phosphorylation of Raf-1 at Ser-43 in chondrocytes.
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掲載誌名 |
Biochemical and Biophysical Research Communications
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ISSN | 0006291X
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cat書誌ID | AA00564395
AA11542044
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出版者 | Elsevier
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巻 | 483
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号 | 1
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開始ページ | 82
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終了ページ | 87
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発行日 | 2017-01-03
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権利情報 | © 2017. This manuscript version is made available under the CC-BY-NC-ND 4.0 license http://creativecommons.org/licenses/by-nc-nd/4.0/
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EDB ID | |
出版社版DOI | |
出版社版URL | |
フルテキストファイル | |
言語 |
eng
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著者版フラグ |
著者版
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部局 |
生物資源系
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