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J Biol Chem, Vol. 274, Issue 2, 703-709, January 8, 1999
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From the An alternatively spliced variant of Smad2 with a
deletion of exon 3 (Smad2 Department of Biochemistry,
exon3) is found in various cell types.
Here, we studied the function of Smad2exon3 and compared it with
those of wild-type Smad2 containing exon 3 (Smad2(wt)) and Smad3. When transcriptional activity was measured using the p3TP-lux construct, Smad2exon3 was more potent than Smad2(wt), and had activity similar to Smad3. Transcriptional activation of the activin-responsive element
(ARE) of Mix.2 gene promoter by Smad2exon3 was also
similar to that by Smad3, and slightly less potent than that by
Smad2(wt). Phosphorylation by the activated transforming growth
factor-
type I receptor and heteromer formation with Smad4 occurred
to similar extents in Smad2exon3, Smad2(wt), and Smad3. However, DNA
binding to the activating protein-1 sites of p3TP-lux was observed in
Smad2exon3 as well as in Smad3, but not in Smad2(wt). In contrast,
Smad2(wt), Smad2exon3, and Smad3 efficiently formed ARE-binding
complexes with Smad4 and FAST1, although Smad2(wt) did not directly
bind to ARE. These results suggest that exon 3 of Smad2 interferes with
the direct DNA binding of Smad2, and modifies the function of Smad2 in
transcription of certain target genes.
Copyright © 1999 by The American Society for Biochemistry and Molecular Biology, Inc.
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