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Roles for lysine residues of the MH2 domain of Smad3 in transforming growth factor-β signaling.

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タイトル: Roles for lysine residues of the MH2 domain of Smad3 in transforming growth factor-β signaling.
著者: Imoto, Seiyu 著作を一覧する
Sugiyama, Kenji 著作を一覧する
Sekine, Yuichi 著作を一覧する
Matsuda, Tadashi 著作を一覧する
キーワード: TGF-β
Mad homology 2 domain
発行日: 2005年 5月23日
出版者: Elsevier
誌名: FEBS Letters
巻: 579
号: 13
開始ページ: 2853
終了ページ: 2862
出版社 DOI: 10.1016/j.febslet.2005.04.023
抄録: Sma and MAD-related protein 3 (Smad3) plays a key role in the intracellular signaling of the transforming growth factor-β (TGF-β) family of growth factors, which exhibits a diverse set of cellular responses, including cell proliferation and differentiation. Smad3 has the N-terminal Mad homology (MH) 1 and the C-terminal MH2 domains. MH2 domain is essential for the TGF-β-induced transcriptional activation, because the MH2 domain of Smad3 is involved in the interactions with several transcriptional cofactors as well as the type I TGF-β receptor (TβR-I). In this study, we examined the roles for four lysine residues (Lys-333, Lys-341, Lys-378, and Lys-409) in the Smad3 MH2 domain. Mutation of the lysine (K)-378 to arginine (R) (K378R) abolished the interaction with TβR-I, phosphorylation, transcriptional activation by an active TβR-I. The K341R mutant also failed to stimulate TGF-β-induced transcription by resting in the cytoplasm. However, the K409R mutant showed a higher transcriptional activity by stronger interactions with co-activators, such as p300/CBP. Furthermore, both the K341R and K378R mutants act as dominant-negative inhibitors in the TGF-β-induced target genes of endogenous TGF-β signal. Thus, the lysine residues of Smad3 MH2 domain play important roles in the transcriptional regulation of TGF-β signals through TβR-I.
Relation (URI):
資料タイプ: article (author version)
出現コレクション:雑誌発表論文等 (Peer-reviewed Journal Articles, etc)

提供者: 松田 正


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