Caenorhabditis elegans Akt/PKB transduces insulin receptor-like signals from AGE-1 PI3 kinase to the DAF-16 transcription factor

Genes Dev. 1998 Aug 15;12(16):2488-98. doi: 10.1101/gad.12.16.2488.

Abstract

A neurosecretory pathway regulates a reversible developmental arrest and metabolic shift at the Caenorhabditis elegans dauer larval stage. Defects in an insulin-like signaling pathway cause arrest at the dauer stage. We show here that two C. elegans Akt/PKB homologs, akt-1 and akt-2, transduce insulin receptor-like signals that inhibit dauer arrest and that AKT-1 and AKT-2 signaling are indispensable for insulin receptor-like signaling in C. elegans. A loss-of-function mutation in the Fork head transcription factor DAF-16 relieves the requirement for Akt/PKB signaling, which indicates that AKT-1 and AKT-2 function primarily to antagonize DAF-16. This is the first evidence that the major target of Akt/PKB signaling is a transcription factor. An activating mutation in akt-1, revealed by a genetic screen, as well as increased dosage of wild-type akt-1 relieves the requirement for signaling from AGE-1 PI3K, which acts downstream of the DAF-2 insulin/IGF-1 receptor homolog. This demonstrates that Akt/PKB activity is not necessarily dependent on AGE-1 PI3K activity. akt-1 and akt-2 are expressed in overlapping patterns in the nervous system and in tissues that are remodeled during dauer formation.

Publication types

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

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Caenorhabditis elegans / genetics
  • Caenorhabditis elegans / physiology*
  • Caenorhabditis elegans Proteins*
  • Forkhead Transcription Factors
  • Gene Expression Regulation, Enzymologic
  • Helminth Proteins / metabolism*
  • Life Expectancy
  • Molecular Sequence Data
  • Mutation
  • Oncogene Proteins / genetics
  • Oncogene Proteins / isolation & purification
  • Oncogene Proteins / physiology
  • Phosphatidylinositol 3-Kinases / metabolism*
  • Phosphatidylinositol 3-Kinases / physiology*
  • Protein-Serine-Threonine Kinases / genetics
  • Protein-Serine-Threonine Kinases / isolation & purification
  • Protein-Serine-Threonine Kinases / physiology
  • Proto-Oncogene Proteins c-akt
  • Proto-Oncogene Proteins*
  • Receptor, Insulin / physiology*
  • Sequence Homology, Amino Acid
  • Signal Transduction*
  • Transcription Factors / physiology*

Substances

  • Caenorhabditis elegans Proteins
  • Forkhead Transcription Factors
  • Helminth Proteins
  • Oncogene Proteins
  • Proto-Oncogene Proteins
  • Transcription Factors
  • daf-16 protein, C elegans
  • Phosphatidylinositol 3-Kinases
  • AGE-1 protein, C elegans
  • DAF-2 protein, C elegans
  • Receptor, Insulin
  • Protein-Serine-Threonine Kinases
  • Proto-Oncogene Proteins c-akt
  • akt-1 protein, C elegans
  • akt-2 protein, C elegans

Associated data

  • GENBANK/AF072379
  • GENBANK/AF072380
  • GENBANK/AF072381