<i>daf-2</i>
            , an Insulin Receptor-Like Gene That Regulates Longevity and Diapause in
            <i>Caenorhabditis elegans</i>

Kimura, Koutarou D.; Tissenbaum, Heidi A.; Liu, Yanxia; Ruvkun, Gary

doi:10.1126/science.277.5328.942

Cited by 2,089 publications

(1,683 citation statements)

References 34 publications

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“…When larvae are grown in sub-optimal conditions, they arrest developmentally and metabolically in a dauer stage. The dauer stage can also be induced by mutations in the IGF/insulin receptor homolog (daf-2) (Kimura et al, 1997), the PI3 kinase homolog (age-1) (Morris et al, 1996) or Akt homologs (akt-1 and akt-2) (Paradis and Ruvkun, 1998). However, if the forkhead homolog daf-16 is mutated, mutations to IGF/insulin receptor, PI3 kinase or Akt homolog do not cause a dauer stage, suggesting the forkhead homolog daf-16 is antagonized by the IGF/insulin-PI3 kinase-Akt pathway (Ogg et al, 1997).…”

Section: Discussionmentioning

confidence: 99%

Phosphorylation and nuclear exclusion of the forkhead transcription factor FKHR after epidermal growth factor treatment in human breast cancer cells

et al. 2000

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Akt, when activated by IGF/insulin, can phosphorylate forkhead transcription factors. We undertook this study to determine whether epidermal growth factor (EGF) treatment could produce a signaling cascade resulting in phosphorylation of the forkhead transcription factor FKHR in a breast cancer cell line, MDA-MB-231. After establishing ErbB1, cbl, PI3 kinase and Akt were activated in EGF treated MDA-MB-231, we determined by immunoblot with FKHR antiserum that the electrophoretic mobility of FKHR was retarded after EGF treatment. This mobility retardation was reversible by treatment with alkaline phosphatase, and immunoblot with phospho-Ser 256 FKHR antibody further con®rmed phosphorylation on an Akt consensus site after EGF treatment. EGF stimulated FKHR phosphorylation was blocked by the PI3 kinase inhibitor LY294002, and the ErbB1 inhibitor AG1478. FKHR immunoblotting after puri®cation of nuclear and cytoplasmic proteins showed that EGF induced a simultaneous increase of FKHR in the cytoplasm and decrease in the nucleus. This ®nding was con®rmed by immuno¯uorescence staining. Treatment of cells with pharmacological inhibitors of PI3 kinase or ErbB1 blocked this e ect. Thus, these results demonstrate the phosphorylation and nuclear exclusion of FKHR after EGF treatment by a PI3 kinase dependent mechanism, and represent the ®rst report of growth factor regulation of endogenous FKHR localization Oncogene (2000) 19, 4574 ± 4581.

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Section: Discussionmentioning

confidence: 99%

Phosphorylation and nuclear exclusion of the forkhead transcription factor FKHR after epidermal growth factor treatment in human breast cancer cells

et al. 2000

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“…The strongest negative correlation with expression profiles of D. melanogaster aging came from profiles of daf-2(e1368) mutants 18 . The gene daf-2 encodes an insulin/IGF-1 receptor homolog; daf-2 mutants age more slowly and live twice as long as wild-type worms 19,20 . D. melanogaster gene expression profiles thus seem to identify both analogous and related gene expression experiments in C. elegans.…”

Section: Biological Processesmentioning

confidence: 99%

Comparing genomic expression patterns across species identifies shared transcriptional profile in aging

et al. 2004

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We developed a method for systematically comparing gene expression patterns across organisms using genome-wide comparative analysis of DNA microarray experiments. We identified analogous gene expression programs comprising shared patterns of regulation across orthologous genes. Biological features of these patterns could be identified as highly conserved subpatterns that correspond to Gene Ontology categories. Here, we demonstrate these methods by analyzing a specific biological process, aging, and show that similar analysis can be applied to a range of biological processes. We found that two highly diverged animals, the nematode Caenorhabditis elegans and the fruit fly Drosophila melanogaster, implement a shared adult-onset expression program of genes involved in mitochondrial metabolism, DNA repair, catabolism, peptidolysis and cellular transport. Most of these changes were implemented early in adulthood. Using this approach to search databases of gene expression data, we found conserved transcriptional signatures in larval development, embryogenesis, gametogenesis and mRNA degradation.Gene expression profiling measures the expression levels of thousands of genes at once 1,2 . Most expression profiling studies have focused on the specific genes that respond to specific conditions, but another important direction in functional genomics is to derive insight from global patterns of gene expression. Genome-scale expression patterns have been used as physiological 'fingerprints' for classifying tumors 3,4 and assigning uncharacterized mutations and drugs to known pathways 5 . Because they use information from many genes at once, patterns have great discriminating power, even when the transcriptional effects on individual genes are small 5,6 .The patterns of changes in gene expression observed in microarray experiments can be extensive and complex. To try to analyze these patterns, we exploited the principle that important biological processes are often conserved between organisms. We present an approach to comparative functional genomics based on shared patterns of regulation across orthologous genes. We also present a method for identifying conserved biological components of those patterns that correspond to Gene Ontology categories. These methods can be used to search databases of microarray experiments to discover connections among biological processes in different organisms. RESULTS Comparing genomic expression patterns across speciesWe used phylogenetic analysis to systematically identify orthologous groups of genes for all pairwise comparisons between C. elegans, D. melanogaster, Saccharomyces cerevisiae and Homo sapiens (Supplementary Tables 1-5 online). For C. elegans and D. melanogaster, we identified 3,851 most-conserved orthologous gene pairs (Fig. 1a).We used DNA microarrays in each organism to compare gene expression under different conditions (Fig. 1b). We then used gene phylogenetic relationships to match systematically the measurements of differential expression between orthologous genes from the tw...

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“…L1 larvae assess levels of this pheromone, as well as levels of food in their environment to make a critical developmental decision. Under overcrowded conditions and low food abundance, animals enter into the dauer developmental stage by downregulating the daf-7 TGF-β and insulin signaling pathways, whereas under conditions more conducive to growth and reproduction, animals proceed in the reproductive cycle [11][12][13][14][15][16][17]. Dauer larvae can reenter the reproductive cycle when conditions improve.…”

Section: The Importance Of Chemosensationmentioning

confidence: 99%

Generation and modulation of chemosensory behaviors in C. elegans

Sengupta

2007

Pflugers Arch - Eur J Physiol

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C. elegans recognizes and discriminates among hundreds of chemical cues using a relatively compact chemosensory nervous system. Chemosensory behaviors are also modulated by prior experience and contextual cues. Because of the facile genetics and genomics possible in this organism, C. elegans provides an excellent system in which to explore the generation of chemosensory behaviors from the level of a single gene to the motor output. This review summarizes the current knowledge on the molecular and neuronal substrates of chemosensory behaviors and chemosensory behavioral plasticity in C. elegans.

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daf-2 , an Insulin Receptor-Like Gene That Regulates Longevity and Diapause in Caenorhabditis elegans

Cited by 2,089 publications

References 34 publications

Phosphorylation and nuclear exclusion of the forkhead transcription factor FKHR after epidermal growth factor treatment in human breast cancer cells

Phosphorylation and nuclear exclusion of the forkhead transcription factor FKHR after epidermal growth factor treatment in human breast cancer cells

Comparing genomic expression patterns across species identifies shared transcriptional profile in aging

Generation and modulation of chemosensory behaviors in C. elegans

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