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Roles for lysine residues of the MH2 domain of Smad3 in transforming growth factor-β signaling.
Title: | Roles for lysine residues of the MH2 domain of Smad3 in transforming growth factor-β signaling. |
Authors: | Imoto, Seiyu Browse this author | Sugiyama, Kenji Browse this author | Sekine, Yuichi Browse this author | Matsuda, Tadashi Browse this author →KAKEN DB |
Keywords: | TGF-β | Smad | Mad homology 2 domain | Lysine | Transcription |
Issue Date: | 23-May-2005 |
Publisher: | Elsevier |
Journal Title: | FEBS Letters |
Volume: | 579 |
Issue: | 13 |
Start Page: | 2853 |
End Page: | 2862 |
Publisher DOI: | 10.1016/j.febslet.2005.04.023 |
PMID: | 15907489 |
Abstract: | 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: | http://www.sciencedirect.com/science/journal/00145793 |
Type: | article (author version) |
URI: | http://hdl.handle.net/2115/28114 |
Appears in Collections: | 薬学研究院 (Faculty of Pharmaceutical Sciences) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)
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Submitter: 松田 正
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