A role for the segment polarity gene shaggy/GSK-3 in the Drosophila circadian clock

被引:438
作者
Martinek, S
Inonog, S
Manoukian, AS
Young, MW [1 ]
机构
[1] Rockefeller Univ, Genet Lab, New York, NY 10021 USA
[2] Rockefeller Univ, Natl Sci Fdn, Sci & Technol Ctr Biol Timing, New York, NY 10021 USA
[3] Ontario Canc Inst, Div Cell & Mol Biol, Toronto, ON M5G 2M9, Canada
关键词
D O I
10.1016/S0092-8674(01)00383-X
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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.
引用
收藏
页码:769 / 779
页数:11
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