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A Role for the Segment Polarity Gene shaggy/GSK-3 in the Drosophila Circadian Clock

pmid: 11440719
A Role for the Segment Polarity Gene shaggy/GSK-3 in the Drosophila Circadian Clock
Tissue-specific overexpression of the glycogen synthase kinase-3 (GSK-3) ortholog shaggy (sgg) shortens the period of the Drosophila circadian locomotor activity cycle. The short period phenotype was attributed to premature nuclear translocation of the PERIOD/TIMELESS heterodimer. Reducing SGG/GSK-3 activity lengthens period, demonstrating an intrinsic role for the kinase in circadian rhythmicity. Lowered sgg activity decreased TIMELESS phosphorylation, and it was found that GSK-3 beta specifically phosphorylates TIMELESS in vitro. Overexpression of sgg in vivo converts hypophosphorylated TIMELESS to a hyperphosphorylated protein whose electrophoretic mobility, and light and phosphatase sensitivity, are indistinguishable from the rhythmically produced hyperphosphorylated TIMELESS of wild-type flies. Our results indicate a role for SGG/GSK-3 in TIMELESS phosphorylation and in the regulated nuclear translocation of the PERIOD/TIMELESS heterodimer.
- Ontario Institute for Cancer Research Canada
- Rockefeller University United States
Cell Nucleus, Biochemistry, Genetics and Molecular Biology(all), Recombinant Fusion Proteins, Immunoblotting, Active Transport, Cell Nucleus, Nuclear Proteins, Period Circadian Proteins, Motor Activity, Protein Serine-Threonine Kinases, Circadian Rhythm, Glycogen Synthase Kinase 3, Drosophila melanogaster, Microscopy, Fluorescence, Biological Clocks, Animals, Drosophila Proteins, Insect Proteins, RNA, Phosphorylation, Dimerization
Cell Nucleus, Biochemistry, Genetics and Molecular Biology(all), Recombinant Fusion Proteins, Immunoblotting, Active Transport, Cell Nucleus, Nuclear Proteins, Period Circadian Proteins, Motor Activity, Protein Serine-Threonine Kinases, Circadian Rhythm, Glycogen Synthase Kinase 3, Drosophila melanogaster, Microscopy, Fluorescence, Biological Clocks, Animals, Drosophila Proteins, Insect Proteins, RNA, Phosphorylation, Dimerization
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