Abstract
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.
Copyright 2001 Academic Press.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Active Transport, Cell Nucleus
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Activin Receptors, Type I*
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Animals
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COS Cells
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Carrier Proteins / metabolism*
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Cell Nucleus / metabolism
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DNA-Binding Proteins / genetics
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DNA-Binding Proteins / metabolism*
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Endosomal Sorting Complexes Required for Transport
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Macromolecular Substances
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Mutation
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Phosphoproteins / genetics
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Phosphoproteins / metabolism
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Phosphorylation
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Protein Serine-Threonine Kinases / genetics
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Protein Serine-Threonine Kinases / metabolism
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Receptor, Transforming Growth Factor-beta Type I
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Receptors, Transforming Growth Factor beta / genetics
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Receptors, Transforming Growth Factor beta / metabolism
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Signal Transduction
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Smad3 Protein
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Trans-Activators / genetics
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Trans-Activators / metabolism*
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Transcriptional Activation
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Transfection
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Transforming Growth Factor beta / physiology*
Substances
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Carrier Proteins
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DNA-Binding Proteins
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Endosomal Sorting Complexes Required for Transport
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Macromolecular Substances
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Phosphoproteins
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Receptors, Transforming Growth Factor beta
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Smad3 Protein
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Trans-Activators
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Transforming Growth Factor beta
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hepatocyte growth factor-regulated tyrosine kinase substrate
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Protein Serine-Threonine Kinases
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Activin Receptors, Type I
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Receptor, Transforming Growth Factor-beta Type I