Goto D, Nakajima H, Mori Y, Kurasawa K, Kitamura N, Iwamoto I
Department of Medicine II, Chiba University School of Medicine, Chiba, Japan.
Biochem Biophys Res Commun. 2001 Mar;281(5):1100-5. doi: 10.1006/bbrc.2001.4489.
Regulation of subcellular localization of Smad proteins is supposed to be critical for the effective initiation and maintenance of TGF-beta signaling. Recently, Smad anchor for receptor activation (SARA) has been identified as a Smad2 binding protein. SARA regulates the subcellular localization of Smad2 and is required for TGF-beta/Smad2-mediated signaling. In this study, we determined whether the interaction between SARA and Smad3 is essential for TGF-beta/Smad3-mediated signaling. We found that a mutant Smad3 (Smad3NS) that lacked the binding to SARA was phosphorylated by TGF-beta type I receptor at the similar level to that in wild-type Smad3 (Smad3WT). Smad3NS also formed complexes with Smad4 and translocalized into the nucleus. Moreover, Smad3NS and Smad3WT equally enhanced TGF-beta-induced transcription. Therefore, these findings indicate that, in contrast to SARA/Smad2 interaction, SARA/Smad3 interaction is not essential for TGF-beta/Smad3-mediated signaling.
Smad蛋白亚细胞定位的调节被认为对TGF-β信号的有效起始和维持至关重要。最近，受体激活的Smad锚定蛋白（SARA）已被鉴定为一种Smad2结合蛋白。SARA调节Smad2的亚细胞定位，并且是TGF-β/Smad2介导信号所必需的。在本研究中，我们确定SARA与Smad3之间的相互作用对于TGF-β/Smad3介导的信号是否至关重要。我们发现，一个缺乏与SARA结合能力的突变型Smad3（Smad3NS）被TGF-β I型受体磷酸化的水平与野生型Smad3（Smad3WT）相似。Smad3NS也与Smad4形成复合物并转位到细胞核中。此外，Smad3NS和Smad3WT同样增强了TGF-β诱导的转录。因此，这些发现表明，与SARA/Smad2相互作用相反，SARA/Smad3相互作用对于TGF-β/Smad3介导的信号并非必不可少。
