ニシマツ　シンイチロウ   Shinichiro Nishimatsu   西松　伸一郎    所属   川崎医科大学  医学部 一般教養　自然科学    職種   教授
論文種別	原著
言語種別	英語
査読の有無	査読あり
表題	Dominant-negative Smad2 mutants inhibit activin/Vg1 signaling and disrupt axis formation in Xenopus.
掲載誌名	正式名：Developmental biology 略　 称：Dev Biol ISSNコード：00121606/1095564X
巻・号・頁	207(2),pp.364-379
著者・共著者	Hoodless Pamela A, Tsukazaki Tomoo, Nishimatsu Shin-ichiro, Attisano Liliana, Wrana Jeffrey L, Thomsent Gerald H
発行年月	1999/03
概要	Smads are central mediators of signal transduction for the TGF superfamily. However, the precise functions of Smad-mediated signaling pathways in early development are unclear. Here we demonstrate a requirement for Smad2 signaling in dorsoanterior axis formation during Xenopus development. Using two point mutations of Smad2 previously identified in colorectal carcinomas, we show that Smad2 ushers Smad4 to the nucleus to form a transcriptional activation complex with the nuclear DNA-binding protein FAST-1 and that the mutant proteins interact normally with FAST-1 but fail to recruit Smad4 into the nucleus. This mechanism of inhibition specifically restricts the dominant-negative activity of these mutants to the activin/Vg1 signaling pathway without inhibiting BMPs. Furthermore, expression of these mutants in Xenopus animal caps inhibits but does not abolish activin and Vg1 induction of mesoderm and in the embryo results in a truncated dorsoanterior axis. These studies define a mechanism through which mutations in Smad2 may block TGFbeta-dependent signaling and suggest a critical role for inductive signaling mediated by the Smad2 pathway in Xenopus organizer function.
DOI	10.1006/dbio.1998.9168
文献番号	10068469