Interaction between Smad anchor for receptor activation and Smad3 is not essential for TGF-beta/Smad3-mediated signaling

Regulation of subcellular localization of Smad proteins is supposed to be c ritical for the effective initiation and maintenance of TGF-beta signaling. Recently, Smad anchor for receptor activation (SARA) has been identified a s a Smad2 binding protein. SARA regulates the subcellular localization of S mad2 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 (Smad3 NS) 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. More over, Smad3NS and Smad3WT equally enhanced TGF-beta -induced transcription. Therefore, these findings indicate that, in contrast to SARA/Smad3 interac tion, SARA/Smad3 interaction is not essential for TGF-beta /Smad3-mediated signaling. (C) 2001 Academic Press.