Tob蛋白增强抑制性Smad受体相互作用以抑制骨形态发生蛋白（BMP）信号传导。

Tob proteins enhance inhibitory Smad-receptor interactions to repress BMP signaling.

作者信息

Yoshida Yutaka, von Bubnoff Andreas, Ikematsu Naoko, Blitz Ira L, Tsuzuku Junko K, Yoshida Eri H, Umemori Hisashi, Miyazono Kohei, Yamamoto Tadashi, Cho Ken W Y

机构信息

Department of Oncology, The Institute of Medical Science, University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108, Japan.

出版信息

Mech Dev. 2003 May;120(5):629-37. doi: 10.1016/s0925-4773(03)00020-0.

DOI:10.1016/s0925-4773(03)00020-0

PMID:12782279

Abstract

Tob inhibits bone morphogenetic protein (BMP) signaling by interacting with receptor-regulated Smads in osteoblasts. Here we provide evidence that Tob also interacts with the inhibitory Smads 6 and 7. A yeast two-hybrid screen identified Smad6 as a protein interacting with Tob. Tob co-localizes with Smad6 at the plasma membrane and enhances the interaction between Smad6 and activated BMP type I receptors. Furthermore, we have isolated Xenopus Tob2, and show that it cooperates with Smad6 in inducing secondary axes when expressed in early Xenopus embryos. Finally, Tob and Tob2 cooperate with Smad6 to inhibit endogenous BMP signaling in Xenopus embryonic explants and in cultured mammalian cells. Our results provide both in vitro and in vivo evidence that Tob inhibits endogenous BMP signaling by facilitating inhibitory Smad functions.

摘要

Tob通过与成骨细胞中受受体调节的Smads相互作用来抑制骨形态发生蛋白（BMP）信号传导。在此，我们提供证据表明Tob还与抑制性Smads 6和7相互作用。酵母双杂交筛选鉴定出Smad6是与Tob相互作用的一种蛋白质。Tob与Smad6在质膜处共定位，并增强Smad6与活化的BMP I型受体之间的相互作用。此外，我们分离出了非洲爪蟾Tob2，并表明当在非洲爪蟾早期胚胎中表达时，它与Smad6协同诱导次级轴。最后，Tob和Tob2与Smad6协同作用，在非洲爪蟾胚胎外植体和培养的哺乳动物细胞中抑制内源性BMP信号传导。我们的结果提供了体外和体内证据，表明Tob通过促进抑制性Smad功能来抑制内源性BMP信号传导。