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

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Please use this identifier to cite or link to this item:http://hdl.handle.net/2115/28114

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)

Submitter: 松田 正

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