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
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Amino Acid Sequence
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Animals
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Caenorhabditis elegans / genetics
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Caenorhabditis elegans / physiology*
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Caenorhabditis elegans Proteins*
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Forkhead Transcription Factors
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Gene Expression Regulation, Enzymologic
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Helminth Proteins / metabolism*
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Life Expectancy
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Molecular Sequence Data
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Mutation
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Oncogene Proteins / genetics
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Oncogene Proteins / isolation & purification
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Oncogene Proteins / physiology
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Phosphatidylinositol 3-Kinases / metabolism*
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Phosphatidylinositol 3-Kinases / physiology*
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Protein Serine-Threonine Kinases / genetics
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Protein Serine-Threonine Kinases / isolation & purification
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Protein Serine-Threonine Kinases / physiology
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Proto-Oncogene Proteins c-akt
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Proto-Oncogene Proteins*
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Receptor, Insulin / physiology*
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Sequence Homology, Amino Acid
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Signal Transduction*
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Transcription Factors / physiology*
Substances
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Caenorhabditis elegans Proteins
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Forkhead Transcription Factors
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Helminth Proteins
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Oncogene Proteins
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Proto-Oncogene Proteins
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Transcription Factors
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daf-16 protein, C elegans
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AGE-1 protein, C elegans
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DAF-2 protein, C elegans
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Receptor, Insulin
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Protein Serine-Threonine Kinases
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Proto-Oncogene Proteins c-akt
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akt-1 protein, C elegans
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akt-2 protein, C elegans
Associated data
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GENBANK/AF072379
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GENBANK/AF072380
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GENBANK/AF072381