Caenorhabditis elegans SOS-1 is necessary for multiple RAS-mediated developmental signals.
Vulval induction in Caenorhabditis elegans has helped define an evolutionarily conserved signal transduction pathway from receptor tyrosine kinases (RTKs) through the adaptor protein SEM-5 to RAS. One component present in other organisms, a guanine nucleotide exchange factor for Ras, has been missing in C.ELEGANS: To understand the regulation of this pathway it is crucial to have all positive-acting components in hand. Here we describe the identification, cloning and genetic characterization of C.ELEGANS: SOS-1, a putative guanine nucleotide exchanger for LET-60 RAS. RNA interference experiments suggest that SOS-1 participates in RAS-dependent signaling events downstream of LET-23 EGFR, EGL-15 FGFR and an unknown RTK. We demonstrate that the previously identified let-341 gene encodes SOS-1. Analyzing vulval development in a let-341 null mutant, we find an SOS-1-independent pathway involved in the activation of RAS signaling. This SOS-1-independent signaling is not inhibited by SLI-1/Cbl and is not mediated by PTP-2/SHP, raising the possibility that there could be another RasGEF.
Chang
C
C
HHMI and Division of Biology, California Institute of Technology, Pasadena, CA 91125, USA.
Hopper
N A
NA
Sternberg
P W
PW
D000483:Alleles; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D017173:Caenorhabditis elegans / Q000196:embryology / Q000235:genetics*; D017931:DNA Primers; D005260:Female; D020690:GTPase-Activating Proteins / Q000378:metabolism; D008024:Ligands; D008969:Molecular Sequence Data; D010641:Phenotype; D012330:RNA, Double-Stranded / Q000008:administration & dosage; D017468:Receptors, Fibroblast Growth Factor / Q000378:metabolism; D020837:SOS1 Protein / Q000235:genetics / Q000502:physiology*; D017386:Sequence Homology, Amino Acid; D015398:Signal Transduction; D014844:Vulva / Q000196:embryology / Q000378:metabolism; D018631:ras Proteins / Q000378:metabolism*
D017931:DNA Primers; D020690:GTPase-Activating Proteins; D008024:Ligands; D012330:RNA, Double-Stranded; D017468:Receptors, Fibroblast Growth Factor; D020837:SOS1 Protein; D018631:ras Proteins