daf-2;par-4

Insulin-like receptor subunit beta;Receptor protein-tyrosine kinase;hypothetical protein

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Locus: CELE_Y55D5A.5

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Wormbase description: daf-2 encodes a receptor tyrosine kinase that is the C. elegans insulin/IGF receptor ortholog; DAF-2 activity is required for a number of processes in C. elegans, including embryonic and larval development, formation of the developmentally arrested dauer larval stage (diapause), larval developmental timing, adult longevity, reproduction, fat storage, salt chemotaxis learning, and stress resistance, including response to high temperature, oxidative stress, and bacterial infection; DAF-2 signals through a conserved PI 3-kinase pathway to negatively regulate the activity of DAF-16, a Forkhead-related transcription factor, by inducing its phosphorylation and nuclear exclusion; in addition, DAF-2 negatively regulates the nuclear localization, and hence transcriptional activity, of SKN-1 in intestinal nuclei; amongst the 38 predicted insulin-like molecules in C. elegans, genetic and microarray analyses suggest that at least DAF-28, INS-1, and INS-7 are likely DAF-2 ligands; genetic mosaic and tissue-specific promoter studies indicate that daf-2 can function cell nonautonomously and within multiple cell types to influence dauer formation and adult lifespan, likely by regulating the production of secondary endocrine signals that coordinate growth and longevity throughout the animal; temporal analysis of daf-2 function indicates that daf-2 regulates lifespan, reproduction, and diapause independently, at distinct times during the animal's life cycle.

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Serine/threonine-protein kinase par-4

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Locus: CELE_Y59A8B.14

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Wormbase description: par-4 encodes a serine-threonine kinase that is homologous to the human LKB1 kinase, mutations in which are associated with the cancer predisposition Peutz-Jeghers syndrome; par-4 activity is required for several development processes, including establishment of embryonic asymmetry, lifespan extension, response to oxidative stress and inhibition of germline proliferation during dauer larvae formation; genetic analyses suggest that in regulating the response to oxidative stress, par-4 acts upstream of aak-2 and that in regulating germ cell proliferation in dauers, par-4 acts upstream of aak-1 and in parallel to aak-2; PAR-4 is present in embryos, L4 larvae, males, and adult hermaphrodites; in the hermaphrodite gonad, PAR-4 is present at the actin-rich boundaries between syncytial nuclei, while in early embryos PAR-4 is present in the cytoplasm and at the cellular cortex; PAR-4 binds bovine calmodulin in vitro in a calcium-dependent manner.

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