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 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.
Department of Medicine II, Chiba University School of Medicine, Chiba, Japan.
D
D
Goto
H
H
Nakajima
Y
Y
Mori
K
K
Kurasawa
N
N
Kitamura
I
I
Iwamoto
D021581:Active Transport, Cell Nucleus; D030201:Activin Receptors, Type I; D000818:Animals; D019556:COS Cells; D002352:Carrier Proteins / Q000378:metabolism*; D002467:Cell Nucleus / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D056827:Endosomal Sorting Complexes Required for Transport; D046911:Macromolecular Substances; D009154:Mutation; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism; D000077293:Receptor, Transforming Growth Factor-beta Type I; D018125:Receptors, Transforming Growth Factor beta / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D051900:Smad3 Protein; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism*; D015533:Transcriptional Activation; D014162:Transfection; D016212:Transforming Growth Factor beta / Q000502:physiology*
D002352:Carrier Proteins; D004268:DNA-Binding Proteins; D056827:Endosomal Sorting Complexes Required for Transport; D046911:Macromolecular Substances; D010750:Phosphoproteins; D018125:Receptors, Transforming Growth Factor beta; D051900:Smad3 Protein; D015534:Trans-Activators; D016212:Transforming Growth Factor beta; C096164:hepatocyte growth factor-regulated tyrosine kinase substrate; D017346:Protein Serine-Threonine Kinases; D030201:Activin Receptors, Type I; D000077293:Receptor, Transforming Growth Factor-beta Type I