Caenorhabditis elegans genes sma-2, sma-3, and sma-4 define a conserved family of transforming growth factor beta pathway components.
Although transforming growth factor beta (TGF-beta) superfamily ligands play critical roles in diverse developmental processes, how cells transduce signals from these ligands is still poorly understood. Cell surface receptors for these ligands have been identified, but their cytoplasmic targets are unknown. We have identified three Caenorhabditis elegans genes, sma-2, sma-3, and sma-4, that have mutant phenotypes similar to those of the TGF-beta-like receptor gene daf-4, indicating that they are required for daf-4-mediated developmental processes. We show that sma-2 functions in the same cells as daf-4, consistent with a role in transducing signals from the receptor. These three genes define a protein family, the dwarfins, that includes the Mad gene product, which participates in the decapentaplegic TGF-beta-like pathway in Drosophila [Sekelsky, J. J., Newfeld, S. J., Raftery, L. A., Chartoff, E. H. & Gelbart, W. M. (1995) Genetics 139, 1347-1358]. The identification of homologous components of these pathways in distantly related organisms suggests that dwarfins may be universally required for TGF-beta-like signal transduction. In fact, we have isolated highly conserved dwarfins from vertebrates, indicating that these components are not idiosyncratic to invertebrates. These analyses suggest that dwarfins are conserved cytoplasmic signal transducers.
Savage
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C
Waksman Institute, Rutgers University, Piscataway, NJ 08855-0759, USA.
Das
P
P
Finelli
A L
AL
Townsend
S R
SR
Sun
C Y
CY
Baird
S E
SE
Padgett
R W
RW
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D017173:Caenorhabditis elegans / Q000196:embryology / Q000235:genetics*; D029742:Caenorhabditis elegans Proteins; D003001:Cloning, Molecular; D017124:Conserved Sequence; D004268:DNA-Binding Proteins / Q000235:genetics; D017238:Genes, Helminth; D015801:Helminth Proteins / Q000235:genetics* / Q000378:metabolism; D008297:Male; D008969:Molecular Sequence Data; D005810:Multigene Family; D018125:Receptors, Transforming Growth Factor beta / Q000235:genetics / Q000378:metabolism; D012097:Repressor Proteins; D017422:Sequence Analysis, DNA; D017386:Sequence Homology, Amino Acid; D015398:Signal Transduction / Q000235:genetics*; D013623:Tail / Q000196:embryology; D014157:Transcription Factors; D016212:Transforming Growth Factor beta / Q000378:metabolism*
D029742:Caenorhabditis elegans Proteins; D004268:DNA-Binding Proteins; D015801:Helminth Proteins; D018125:Receptors, Transforming Growth Factor beta; D012097:Repressor Proteins; D014157:Transcription Factors; D016212:Transforming Growth Factor beta; C083704:daf-4 protein, C elegans; C097873:sma-2 protein, C elegans; C097874:sma-3 protein, C elegans; C097875:sma-4 protein, C elegans