The C. elegans PTEN homolog, DAF-18, acts in the insulin receptor-like metabolic signaling pathway

Mol Cell. 1998 Dec;2(6):887-93. doi: 10.1016/s1097-2765(00)80303-2.

Abstract

An insulin-like signaling pathway, from the DAF-2 receptor, the AGE-1 phosphoinositide 3-kinase, and the AKT-1/AKT-2 serine/threonine kinases to the DAF-16 Fork head transcription factor, regulates the metabolism, development, and life span of Caenorhabditis elegans. Inhibition of daf-18 gene activity bypasses the normal requirement for AGE-1 and partially bypasses the need for DAF-2 signaling. The suppression of age-1 mutations by a daf-18 mutation depends on AKT-1/AKT-2 signaling, showing that DAF-18 acts between AGE-1 and the AKT input to DAF-16 transcriptional regulation. daf-18 encodes a homolog of the human tumor suppressor PTEN (MMAC1/TEP1), which has 3-phosphatase activity toward phosphatidylinositol 3,4,5-trisphosphate (PIP3). DAF-18 PTEN may normally limit AKT-1 and AKT-2 activation by decreasing PIP3 levels. The action of daf-18 in this metabolic control pathway suggests that mammalian PTEN may modulate insulin signaling and may be variant in diabetic pedigrees.

Publication types

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

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Base Sequence
  • Caenorhabditis elegans / chemistry
  • Caenorhabditis elegans / genetics
  • Caenorhabditis elegans / physiology*
  • Caenorhabditis elegans Proteins*
  • Epistasis, Genetic
  • Gene Expression Regulation
  • Genes, Helminth / genetics
  • Helminth Proteins / genetics
  • Helminth Proteins / physiology*
  • Larva / genetics
  • Molecular Sequence Data
  • PTEN Phosphohydrolase
  • Phenotype
  • Phosphatidylinositol 3-Kinases*
  • Phosphoric Monoester Hydrolases / genetics*
  • Protein-Serine-Threonine Kinases / genetics
  • Proto-Oncogene Proteins / genetics
  • Proto-Oncogene Proteins c-akt
  • RNA, Double-Stranded / genetics
  • RNA, Helminth / genetics
  • Receptor, Insulin / genetics
  • Receptor, Insulin / physiology*
  • Sequence Homology, Amino Acid
  • Signal Transduction
  • Tumor Suppressor Proteins*

Substances

  • Caenorhabditis elegans Proteins
  • DAF-18 protein, C elegans
  • Helminth Proteins
  • Proto-Oncogene Proteins
  • RNA, Double-Stranded
  • RNA, Helminth
  • Tumor Suppressor Proteins
  • 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
  • Phosphoric Monoester Hydrolases
  • PTEN Phosphohydrolase

Associated data

  • GENBANK/AF098286