Regulation of DAF-2 receptor signaling by human insulin and ins-1, a member of the unusually large and diverse C. elegans insulin gene family
| Autor: | Darren Mark Platt, Jonathan Heller, Kimberly Carr Ferguson, Sharmila Devadhar, Sheila A. Homburger, Leo X. Liu, Andrew Roy Buchman, Stephen Kohl Doberstein, Michael Costa, Amy A. Pasquinelli, Gary Ruvkun, Sarah B. Pierce, Robert G. Wisotzkey |
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| Rok vydání: | 2001 |
| Předmět: |
Time Factors
Recombinant Fusion Proteins medicine.medical_treatment Molecular Sequence Data Animals Genetically Modified Genetics medicine Animals Humans Insulin Amino Acid Sequence Cloning Molecular Caenorhabditis elegans Caenorhabditis elegans Proteins Promoter Regions Genetic Gene Models Genetic Sequence Homology Amino Acid biology fungi Temperature Helminth Proteins biology.organism_classification Phenotype Receptor Insulin Protein Structure Tertiary Dauer entry Enhancer Elements Genetic Microscopy Fluorescence Regulatory sequence Mutation Daf-2 Signal transduction Gene Deletion Signal Transduction Research Paper Developmental Biology |
| Zdroj: | Genes & Development. 15:672-686 |
| ISSN: | 1549-5477 0890-9369 |
| DOI: | 10.1101/gad.867301 |
| Popis: | The activity of the DAF-2 insulin-like receptor is required forCaenorhabditis elegans reproductive growth and normal adult life span. Informatic analysis identified 37 C. elegans genes predicted to encode insulin-like peptides. Many of these genes are divergent insulin superfamily members, and many are clustered, indicating recent diversification of the family. The ins genes are primarily expressed in neurons, including sensory neurons, a subset of which are required for reproductive development. Structural predictions and likely C-peptide cleavage sites typical of mammalian insulins suggest that ins-1 is most closely related to insulin. Overexpression of ins-1, or expression of human insulin under the control of ins-1 regulatory sequences, causes partially penetrant arrest at the dauer stage and enhances dauer arrest in weakdaf-2 mutants, suggesting that INS-1 and human insulin antagonize DAF-2 insulin-like signaling. A deletion of theins-1 coding region does not enhance or suppress dauer arrest, indicating a functional redundancy among the 37 ins genes. Of five other ins genes tested, the only other one bearing a predicted C peptide also antagonizes daf-2 signaling, whereas four ins genes without a C peptide do not, indicating functional diversity within the ins family. |
| Databáze: | OpenAIRE |
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