ID | 111887 |
Author |
Murakami, Sara
Tokushima University
Komatsu, Hiroaki
Tokushima University
Sawanoi, Masahiro
Tokushima University
Miyamoto, Kenji
Tokushima University
Ishidoh, Kazumi
Tokushima University
Kishimoto, Koji
Tokushima University
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Tsuji, Akihiko
Tokushima University
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|
Keywords | PKGII
Raf-1
Chondrocytes
FGF
|
Content Type |
Journal Article
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Description | 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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Journal Title |
Biochemical and Biophysical Research Communications
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ISSN | 0006291X
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NCID | AA00564395
AA11542044
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Publisher | Elsevier
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Volume | 483
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Issue | 1
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Start Page | 82
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End Page | 87
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Published Date | 2017-01-03
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Rights | © 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 | |
DOI (Published Version) | |
URL ( Publisher's Version ) | |
FullText File | |
language |
eng
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TextVersion |
Author
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departments |
Bioscience and Bioindustry
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