Caenorhabditis elegans SOS-1 is necessary for multiple RAS-mediated developmental signals

EMBO J. 2000 Jul 3;19(13):3283-94. doi: 10.1093/emboj/19.13.3283.

Abstract

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.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Alleles
  • Amino Acid Sequence
  • Animals
  • Base Sequence
  • Caenorhabditis elegans / embryology
  • Caenorhabditis elegans / genetics*
  • DNA Primers
  • Female
  • GTPase-Activating Proteins / metabolism
  • Ligands
  • Molecular Sequence Data
  • Phenotype
  • RNA, Double-Stranded / administration & dosage
  • Receptors, Fibroblast Growth Factor / metabolism
  • SOS1 Protein / genetics
  • SOS1 Protein / physiology*
  • Sequence Homology, Amino Acid
  • Signal Transduction*
  • Vulva / embryology
  • Vulva / metabolism
  • ras Proteins / metabolism*

Substances

  • DNA Primers
  • GTPase-Activating Proteins
  • Ligands
  • RNA, Double-Stranded
  • Receptors, Fibroblast Growth Factor
  • SOS1 Protein
  • ras Proteins