The C. elegans PTEN homolog, DAF-18, acts in the insulin receptor-like metabolic signaling pathway.
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.
Ogg
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Department of Molecular Biology, Massachusetts General Hospital, Boston 02114, USA.
Ruvkun
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D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D017173:Caenorhabditis elegans / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D029742:Caenorhabditis elegans Proteins; D004843:Epistasis, Genetic; D005786:Gene Expression Regulation; D017238:Genes, Helminth / Q000235:genetics; D015801:Helminth Proteins / Q000235:genetics / Q000502:physiology*; D007814:Larva / Q000235:genetics; D008969:Molecular Sequence Data; D051059:PTEN Phosphohydrolase; D010641:Phenotype; D019869:Phosphatidylinositol 3-Kinases; D010744:Phosphoric Monoester Hydrolases / Q000235:genetics*; D017346:Protein Serine-Threonine Kinases / Q000235:genetics; D011518:Proto-Oncogene Proteins / Q000235:genetics; D051057:Proto-Oncogene Proteins c-akt; D012330:RNA, Double-Stranded / Q000235:genetics; D018510:RNA, Helminth / Q000235:genetics; D011972:Receptor, Insulin / Q000235:genetics / Q000502:physiology*; D017386:Sequence Homology, Amino Acid; D015398:Signal Transduction; D025521:Tumor Suppressor Proteins
D029742:Caenorhabditis elegans Proteins; D015801:Helminth Proteins; D051059:PTEN Phosphohydrolase; D019869:Phosphatidylinositol 3-Kinases; D010744:Phosphoric Monoester Hydrolases; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins; D051057:Proto-Oncogene Proteins c-akt; D012330:RNA, Double-Stranded; D018510:RNA, Helminth; D011972:Receptor, Insulin; D025521:Tumor Suppressor Proteins; C116661:DAF-18 protein, C elegans; C100662:AGE-1 protein, C elegans; C107483:DAF-2 protein, C elegans; C494915:akt-1 protein, C elegans; C494916:akt-2 protein, C elegans