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PMID:11440719
| Citation |
Martinek, S, Inonog, S, Manoukian, AS and Young, MW (2001) A role for the segment polarity gene shaggy/GSK-3 in the Drosophila circadian clock. Cell 105:769-79 |
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| Abstract |
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. |
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| Keywords |
Active Transport, Cell Nucleus; Animals; Biological Clocks/genetics; Biological Clocks/physiology; Cell Nucleus/metabolism; Circadian Rhythm/genetics; Circadian Rhythm/physiology; Dimerization; Drosophila Proteins; Drosophila melanogaster/embryology; Drosophila melanogaster/genetics; Drosophila melanogaster/physiology; Glycogen Synthase Kinase 3; Immunoblotting; Insect Proteins/genetics; Insect Proteins/metabolism; Microscopy, Fluorescence; Motor Activity/genetics; Motor Activity/physiology; Nuclear Proteins/metabolism; Period Circadian Proteins; Phosphorylation; Protein-Serine-Threonine Kinases/genetics; Protein-Serine-Threonine Kinases/metabolism; RNA/genetics; RNA/metabolism; Recombinant Fusion Proteins/genetics; Recombinant Fusion Proteins/metabolism |
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Significance
Annotations
| Gene product | Qualifier | GO ID | GO term name | Evidence Code | with/from | Aspect | Notes | Status |
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