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千葉大学学術成果リポジトリ
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2025-11-02
11:32 集計
)
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e202503300.full
pdf
14.2 MB
4
SourceDataforFigS1
xlsx
12.6 KB
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SourceDataforFig1-1
pdf
635 KB
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SourceDataforFig1-2
xlsx
20.1 KB
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SourceDataforFig2-1
pdf
1.31 MB
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SourceDataforFig2-2
xlsx
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SourceDataforFig3
xlsx
151 KB
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SourceDataforFig4-1
pdf
498 KB
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SourceDataforFig4-2
xlsx
83.3 KB
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SourceDataforFig4B
pse
1.08 MB
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SourceDataforFig5-1
pdf
562 KB
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SourceDataforFig5-2
xlsx
53.7 KB
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SourceDataforFig6
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SourceDataforFig7
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Reviewer-comments
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基本情報
データ種別:学術成果リポジトリ
タイトル
DA-Raf synergistically binds to the plasma membrane and Ras to suppress ERK signaling
作成者
TAKANO, Kazunori
TSUJITA, Kazuya
SUGANAMI, Akiko
NAKAMURA, Takuhiko
KANNO, Emiri
TAMURA, Yutaka
ITOH, Toshiki
ENDO, Takeshi
キーワード等
Plasma Membrane
MAP Kinase Signaling
K-Ras Protein
Lipid-Protein Binding
Proto-Oncogene Protein Kinases A/B/C-Raf
DA-Raf Protein
内容
[Abstract] The small GTPase Ras on the plasma membrane (PM) activates the ERK pathway (Raf-MEK-ERK signaling pathway) to regulate a variety of cellular, physiological, and pathological events. DA-Raf1 (DA-Raf) is a splicing isoform of A-Raf and contains the Ras-binding domain and the Cys-rich domain but lacks the conserved region 2 (CR2) and CR3 containing the kinase domain. Accordingly, DA-Raf dominant-negatively regulates Raf proteins to prevent the Ras-ERK pathway. We elucidate here the mechanisms of how DA-Raf conducts its dominant-negative function on Raf proteins. Because DA-Raf lacks the CR2 and CR3, it was incapable of adopting the autoinhibitory closed conformation and thereby favorable for PM localization. Basic amino acids in DA-Raf Ras-binding domain, and those in the Cys-rich domain, were essential for the interaction with phosphatidylserine in the PM. This interaction favored the cooperative binding of DA-Raf to active Ras, which predominated over that of Raf proteins, leading to the stable PM association of DA-Raf. Consequently, DA-Raf exerts its dominant-negative function on Raf proteins to prevent the Ras-ERK pathway.
ハンドルURL
https://opac.ll.chiba-u.jp/da/curator/900123437/
フルテキストへのリンク
https://opac.ll.chiba-u.jp/da/curator/900123437/e202503300.full.pdf
https://opac.ll.chiba-u.jp/da/curator/900123437/SourceDataforFigS1.xlsx
https://opac.ll.chiba-u.jp/da/curator/900123437/SourceDataforFig1-1.pdf
https://opac.ll.chiba-u.jp/da/curator/900123437/SourceDataforFig1-2.xlsx
https://opac.ll.chiba-u.jp/da/curator/900123437/SourceDataforFig2-1.pdf
https://opac.ll.chiba-u.jp/da/curator/900123437/SourceDataforFig2-2.xlsx
https://opac.ll.chiba-u.jp/da/curator/900123437/SourceDataforFig3.xlsx
https://opac.ll.chiba-u.jp/da/curator/900123437/SourceDataforFig4-1.pdf
https://opac.ll.chiba-u.jp/da/curator/900123437/SourceDataforFig4-2.xlsx
https://opac.ll.chiba-u.jp/da/curator/900123437/SourceDataforFig4B.pse
https://opac.ll.chiba-u.jp/da/curator/900123437/SourceDataforFig5-1.pdf
https://opac.ll.chiba-u.jp/da/curator/900123437/SourceDataforFig5-2.xlsx
https://opac.ll.chiba-u.jp/da/curator/900123437/SourceDataforFig6.xlsx
https://opac.ll.chiba-u.jp/da/curator/900123437/SourceDataforFig7.xlsx
https://opac.ll.chiba-u.jp/da/curator/900123437/Reviewer-comments.pdf
公開者
Life Science Alliance LLC
NII資源タイプ
学術雑誌論文
ISSN
25751077
掲載誌名
Life Science Alliance
巻
8
号
12
開始ページ
e202503300
刊行年月
2025
DOI(出版者版)
10.26508/lsa.202503300
著者版フラグ
publisher
カテゴリ
PubMed 収録論文 (PMC除く)
権利関係
©2025 Takano et al.
This article is available under a Creative Commons License (Attribution 4.0 International, as described at https://creativecommons.org/licenses/by/4.0/).
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DCMI資源タイプ
text
ファイル形式 [IMT]
application/pdf
PubMedID
41120211
言語 [ISO639-2]
eng
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