| First Author | Yanagi Y | Year | 1999 |
| Journal | J Biol Chem | Volume | 274 |
| Issue | 19 | Pages | 12971-4 |
| PubMed ID | 10224044 | Mgi Jnum | J:54891 |
| Mgi Id | MGI:1336564 | Doi | 10.1074/jbc.274.19.12971 |
| Citation | Yanagi Y, et al. (1999) Positive and negative modulation of vitamin D receptor function by transforming growth factor-beta signaling through smad proteins. J Biol Chem 274(19):12971-4 |
| abstractText | 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. |
