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Insulin receptor substrate and p55 orthologous adaptor proteins function in the Caenorhabditis elegans daf-2/insulin-like signaling pathway.

An insulin-like signaling pathway regulates development and lifespan in Caenorhabditis elegans. Genetic screens that identified many components of the C. elegans insulin pathway did not identify homologs of insulin receptor substrates or the phosphoinositide 3-kinase (PI3K) adaptor/regulatory subunit, which are both required for signaling by mammalian insulin/insulin-like growth factor I pathways. The C. elegans genome contains one homolog of each protein. The C. elegans versions of insulin receptor substrate (IST-1) and PI3K p50/p55 (AAP-1) share moderate sequence similarity with their vertebrate and Drosophila counterparts. Genetic experiments show that ist-1 and aap-1 potentiate C. elegans insulin-like signaling, although they are not required for signaling in the pathway under most conditions. Worms lacking AAP-1 activity because of the mutation aap-1(m889) constitutively arrest development at the dauer larval stage when raised at high temperatures. aap-1 mutants also live longer than wild-type animals, a phenotype observed in other C. elegans mutants with defects in DAF-2 signaling. Interestingly, IST-1 appears to be required for signaling through a pathway that may act in parallel to AGE-1/PI3K.

Pubmed ID: 12393910


  • Wolkow CA
  • Muñoz MJ
  • Riddle DL
  • Ruvkun G


The Journal of biological chemistry

Publication Data

December 20, 2002

Associated Grants

  • Agency: NIA NIH HHS, Id: AG 12689
  • Agency: NIA NIH HHS, Id: AG 14161
  • Agency: NIGMS NIH HHS, Id: GM 60151
  • Agency: Intramural NIH HHS, Id: NIH0011061953
  • Agency: NIA NIH HHS, Id: R01 AG014161
  • Agency: Intramural NIH HHS, Id: Z01 AG000320-06

Mesh Terms

  • Amino Acid Sequence
  • Animals
  • Binding Sites
  • Caenorhabditis elegans
  • Caenorhabditis elegans Proteins
  • Cloning, Molecular
  • Codon, Nonsense
  • DNA, Complementary
  • Insulin Receptor Substrate Proteins
  • Models, Biological
  • Models, Genetic
  • Molecular Sequence Data
  • Mutation
  • Phosphatidylinositol 3-Kinases
  • Phosphoproteins
  • Phosphorylation
  • Protein Binding
  • Protein Kinases
  • Protein Structure, Tertiary
  • RNA Interference
  • Receptor, Insulin
  • Sequence Homology, Amino Acid
  • Signal Transduction
  • Temperature