Specificity of TGFbeta signaling is conferred by distinct type I receptors and their associated SMAD proteins in Caenorhabditis elegans.
In C. elegans, the TGFbeta-like type II receptor daf-4 is required for two distinct signaling pathways. In association with the type I receptor daf-1, it functions in the dauer pathway. In addition, it is also required for body size determination and male tail patterning, roles which do not require daf-1. In an effort to determine how two different signals are transmitted through daf-4, we looked for other potential signaling partners for DAF-4. We have cloned and characterized a novel type I receptor and show that it is encoded by sma-6. Mutations in sma-6 generate the reduced body size (Sma) and abnormal mail tail (Mab) phenotypes identical to those observed in daf-4 and sma-2, sma-3, sma-4 mutants (C. elegans Smads), indicating that they function in a common signaling pathway. However, mutations in sma-6, sma-2, sma-3, or sma-4 do not produce constitutive dauers, which demonstrates that the unique biological functions of daf-4 are mediated by distinct type I receptors functioning in parallel pathways. We propose that the C. elegans model for TGFbeta-like signaling, in which distinct type I receptors determine specificity, may be a general mechanism of achieving specificity in other organisms. These findings distinguish between the manner in which signaling specificity is achieved in TGFbeta-like pathways and receptor tyrosine-kinase (RTK) pathways.
Krishna
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S
Waksman Institute, Department of Molecular Biology and Biochemistry, Rutgers University, Piscataway, NJ 08854-8020, USA.
Maduzia
L L
LL
Padgett
R W
RW
D030201:Activin Receptors, Type I; D000483:Alleles; D000595:Amino Acid Sequence; D000818:Animals; D030801:Animals, Genetically Modified; D001824:Body Constitution / Q000235:genetics; D019521:Body Patterning / Q000235:genetics; D052005:Bone Morphogenetic Protein Receptors, Type I; D017173:Caenorhabditis elegans / Q000254:growth & development*; D029742:Caenorhabditis elegans Proteins; D003001:Cloning, Molecular; D018507:Gene Expression Regulation, Developmental; D015801:Helminth Proteins / Q000235:genetics; D008297:Male; D008969:Molecular Sequence Data; D010641:Phenotype; D017346:Protein Serine-Threonine Kinases / Q000235:genetics*; D000077293:Receptor, Transforming Growth Factor-beta Type I; D011956:Receptors, Cell Surface / Q000235:genetics*; D017978:Receptors, Growth Factor / Q000235:genetics*; D018125:Receptors, Transforming Growth Factor beta / Q000235:genetics*; D016415:Sequence Alignment; D017422:Sequence Analysis, DNA; D015398:Signal Transduction / Q000235:genetics*; D013623:Tail / Q000254:growth & development*; D016212:Transforming Growth Factor beta / Q000378:metabolism*
D029742:Caenorhabditis elegans Proteins; D015801:Helminth Proteins; D011956:Receptors, Cell Surface; D017978:Receptors, Growth Factor; D018125:Receptors, Transforming Growth Factor beta; C117510:SMA-6 protein, C elegans; D016212:Transforming Growth Factor beta; C083704:daf-4 protein, C elegans; D017346:Protein Serine-Threonine Kinases; D030201:Activin Receptors, Type I; D052005:Bone Morphogenetic Protein Receptors, Type I; D000077293:Receptor, Transforming Growth Factor-beta Type I