Shinichiro Nishimatsu    Department   Kawasaki Medical School  Kawasaki Medical School, Department of Natural Sciences,    Position   Professor
Article types	原著
Language	English
Peer review	Peer reviewed
Title	Dominant-negative Smad2 mutants inhibit activin/Vg1 signaling and disrupt axis formation in Xenopus.
Journal	Formal name：Developmental biology Abbreviation：Dev Biol ISSN code：00121606/1095564X
Volume, Issue, Page	207(2),pp.364-379
Author and coauthor	Hoodless Pamela A, Tsukazaki Tomoo, Nishimatsu Shin-ichiro, Attisano Liliana, Wrana Jeffrey L, Thomsent Gerald H
Publication date	1999/03
Summary	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
Document No.	10068469