ARK-1 inhibits EGFR signaling in C. elegans

Mol Cell. 2000 Jul;6(1):65-75.


A screen for synthetic enhancers of sli-1 identified ark-1 (forAck-related tyrosine kinase), a novel inhibitor of let-23 EGFR signaling in C. elegans. An ark-1 mutation synergizes with mutations in other negative regulators of let-23, resulting in increased RAS signaling. Genetic analysis suggests that ARK-1 acts upstream of RAS and is dependent upon SEM-5. ARK-1 inhibits LET-23-mediated ovulation, a RAS-independent function. ARK-1 physically interacts with SEM-5 in the yeast two-hybrid assay. We find that sem-5 also has a negative function in let-23-mediated ovulation and suggest that this negative function is mediated by the recruitment of inhibitors such as ARK-1.

Publication types

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

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Caenorhabditis elegans / genetics
  • Caenorhabditis elegans / growth & development
  • Caenorhabditis elegans / metabolism*
  • Caenorhabditis elegans Proteins*
  • Cloning, Molecular
  • ErbB Receptors / metabolism*
  • Female
  • Fertility / physiology
  • Genes, Helminth
  • Genes, Lethal
  • Genes, ras
  • Helminth Proteins / metabolism*
  • Models, Biological
  • Molecular Sequence Data
  • Mutation
  • Ovulation / physiology
  • Protein-Tyrosine Kinases / genetics
  • Protein-Tyrosine Kinases / metabolism*
  • Sequence Homology, Amino Acid
  • Signal Transduction
  • Two-Hybrid System Techniques
  • Vulva / growth & development


  • Caenorhabditis elegans Proteins
  • Helminth Proteins
  • Ack-related tyrosine kinase-1, C elegans
  • ErbB Receptors
  • Protein-Tyrosine Kinases
  • let-23 protein, C elegans

Associated data

  • GENBANK/AJ271057