The mechanisms by which transforming growth factor beta (TGF-beta) and rela
ted ligands regulate transcription remain poorly understood. The winged-hel
ix (WH) transcription factor fork head activin signal transducer 1 (FAST-1)
was identified as a mediator of activin signaling in Xenopus embryos (X, C
hen, M, J, Rubock, and M. Whitman, Nature 383:691-696, 1996), We have clone
d a novel WH gene from the mouse which shares many properties with FAST-1,
We find that this gene, which we call FAST-2, is able to mediate transcript
ional activation by TGF-beta, FAST-2 also interacts directly with Smad2, a
cytoplasmic protein which is translocated to the nucleus in response to TGF
-beta, and forms a multimeric complex with Smad2 and Smad4 on the activin r
esponse element, a high-affinity binding site for FAST-1, Analysis of the s
equences of FAST-1 and FAST-2 reveals substantial protein sequence divergen
ce compared to known vertebrate orthologs in the WH family. This suggests t
hat FAST-2 represents a new WH gene related to FAST-1, which functions to m
ediate TGF-beta signals in mammals. We have also examined the structure of
the FAST-2 gene and find that it overlaps with a kinesin motor protein gene
, The genes are transcribed in opposite orientations, and their transcripts
overlap in the 3' untranslated region.