SUR-8, a conserved Ras-binding protein with leucine-rich repeats, positively regulates Ras-mediated signaling in C. elegans

Cell. 1998 Jul 10;94(1):119-30. doi: 10.1016/s0092-8674(00)81227-1.

Abstract

We describe the identification and characterization of a novel gene, sur-8, that positively regulates Ras-mediated signal transduction during C. elegans vulval development. Reduction of sur-8 function suppresses an activated ras mutation and dramatically enhances phenotypes of mpk-1 MAP kinase and ksr-1 mutations, while increase of sur-8 dosage enhances an activated ras mutation. sur-8 appears to act downstream of or in parallel to ras but upstream of raf. sur-8 encodes a conserved protein that is composed predominantly of leucine-rich repeats. The SUR-8 protein interacts directly with Ras but not with the Ras(P34G) mutant protein, suggesting that SUR-8 may mediate its effects through Ras binding. A structural and functional SUR-8 homolog in humans specifically binds K-Ras and N-Ras but not H-Ras in vitro.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adaptor Proteins, Signal Transducing*
  • Amino Acid Sequence
  • Animals
  • Caenorhabditis elegans / embryology
  • Caenorhabditis elegans / genetics*
  • Caenorhabditis elegans Proteins*
  • Carrier Proteins / genetics*
  • Conserved Sequence
  • Embryonic Induction
  • Female
  • Gene Dosage
  • Genes, Helminth*
  • Leucine
  • Mammals / genetics
  • Mitogen-Activated Protein Kinase 1
  • Molecular Sequence Data
  • Mutation
  • Phenotype
  • Protein Binding
  • Protein Kinases / genetics
  • Protein-Serine-Threonine Kinases / genetics
  • Proto-Oncogene Proteins c-raf / metabolism
  • Repetitive Sequences, Nucleic Acid
  • Sequence Homology, Amino Acid
  • Signal Transduction
  • Suppression, Genetic
  • Vulva / embryology
  • ras Proteins / metabolism*

Substances

  • Adaptor Proteins, Signal Transducing
  • Caenorhabditis elegans Proteins
  • Carrier Proteins
  • soc-2 protein, C elegans
  • let-60 protein, C elegans
  • Protein Kinases
  • KSR-1 protein kinase
  • Protein-Serine-Threonine Kinases
  • Proto-Oncogene Proteins c-raf
  • Mitogen-Activated Protein Kinase 1
  • mpk-1 protein, C elegans
  • ras Proteins
  • Leucine

Associated data

  • GENBANK/AF068919
  • GENBANK/AF068920
  • GENBANK/AF068921