Yanagi Y, Suzawa M, Kawabata M, Miyazono K, Yanagisawa J, Kato S
Institute of Molecular and Cellular Biosciences, University of Tokyo, Yayoi 1-1-1, Bunkyo-ku, Tokyo 113-0034, Japan.
J Biol Chem. 1999 May 7;274(19):12971-4. doi: 10.1074/jbc.274.19.12971.
Several lines of experiments demonstrated the interplay between the transforming growth factor-beta (TGF-beta) and vitamin D signaling pathways. Recently, we found that Smad3, a downstream component of the TGF-beta signaling pathway, potentiates ligand-induced transactivation of vitamin D receptor (VDR) as a coactivator of VDR (Yanagisawa, J., Yanagi, Y., Masuhiro, Y., Suzawa, M., Watanabe, M., Kashiwagi, K., Toriyabe, T., Kawabata, M., Miyazono, K., and Kato, S. (1999) Science 283, 1317-1321). Here, we investigated the roles of inhibitory Smads, Smad6 and Smad7, which are negative regulators of the TGF-beta/bone morphogenetic protein signaling pathway, on the Smad3-mediated potentiation of VDR function. We found that Smad7, but not Smad6, abrogates the Smad3-mediated VDR potentiation. Interaction studies in vivo and in vitro showed that Smad7 inhibited the formation of the VDR-Smad3 complex, whereas Smad6 had no effect. Taken together, our results strongly suggest that the interplay between the TGF-beta and vitamin D signaling pathways is, at least in part, mediated by the two classes of Smad proteins, which modulate VDR transactivation function both positively and negatively.
多项实验表明转化生长因子-β（TGF-β）与维生素D信号通路之间存在相互作用。最近，我们发现TGF-β信号通路的下游成分Smad3作为维生素D受体（VDR）的共激活因子增强配体诱导的VDR反式激活（柳泽纯一、柳井洋、增广洋、铃木正、渡边正、柏木和、鸟矢部彻、川端真、宫园和、加藤修（1999年）《科学》283卷，第1317 - 1321页）。在此，我们研究了TGF-β/骨形态发生蛋白信号通路的负调控因子抑制性Smads，即Smad6和Smad7，对Smad3介导的VDR功能增强作用的影响。我们发现Smad7而非Smad6消除了Smad3介导的VDR增强作用。体内和体外相互作用研究表明，Smad7抑制VDR - Smad3复合物的形成，而Smad6没有影响。综上所述，我们的结果强烈表明TGF-β与维生素D信号通路之间的相互作用至少部分是由两类Smad蛋白介导的，它们对VDR反式激活功能具有正向和负向调节作用。
