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- Title
Arkadia amplifies TGF-β superfamily signalling through degradation of Smad7.
- Authors
Daizo Koinuma; Masahiko Shinozaki; Akiyoshi Komuro; Kouichiro Goto; Masao Saitoh; Aki Hanyu; Masahito Ebina; Toshihiro Nukiwa; Keiji Miyazawa; Takeshi Imamura; Kohei Miyazono
- Abstract
Arkadia was originally identified as a protein that enhances signalling activity of Nodal and induces mammalian nodes during early embryogenesis; however, the mechanisms by which Arkadia affects transforming growth factor-β (TGF-β) superfamily signalling have not been determined. Here we show that Arkadia is widely expressed in mammalian tissues, and that it enhances both TGF-β and bone morphogenetic protein (BMP) signalling. Arkadia physically interacts with inhibitory Smad, Smad7, and induces its poly-ubiquitination and degradation. In contrast to Smurf1, which interacts with TGF-β receptor complexes through Smad7 and degrades them, Arkadia fails to associate with TGF-β receptors. In contrast to Smad7, expression of Arkadia is down-regulated by TGF-β. Silencing of the Arkadia gene resulted in repression of transcriptional activities induced by TGF-β and BMP, and accumulation of the Smad7 protein. Arkadia may thus play an important role as an amplifier of TGF-β superfamily signalling under both physiological and pathological conditions.
- Publication
EMBO Journal, 2003, Vol 22, Issue 24, p6458
- ISSN
0261-4189
- Publication type
Academic Journal
- DOI
10.1093/emboj/cdg632