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Rapid activation of CLOCK by Ca 2+ ‐dependent protein kinase C mediates resetting of the mammalian circadian clock
Author(s) -
Shim Hong Seok,
Kim Hyunjung,
Lee Jiwon,
Son Gi Hoon,
Cho Sehyung,
Oh Tae H,
Kang Sang Hyeon,
Seen DongSeung,
Lee Kun Ho,
Kim Kyungjin
Publication year - 2007
Publication title -
embo reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.584
H-Index - 184
eISSN - 1469-3178
pISSN - 1469-221X
DOI - 10.1038/sj.embor.7400920
Subject(s) - circadian clock , per1 , protein kinase c , microbiology and biotechnology , biology , clock , phosphorylation , circadian rhythm , endocrinology
In mammals, immediate‐early transcription of the Period 1 ( Per1 ) gene is crucial for resetting the mammalian circadian clock. Here, we show that CLOCK is a real signalling molecule that mediates the serum‐evoked rapid induction of Per1 in fibroblasts through the Ca 2+ ‐dependent protein kinase C (PKC) pathway. Stimulation with serum rapidly induced nuclear translocation, heterodimerization and Ser/Thr phosphorylation of CLOCK just before the surge of Per1 transcription. Serum‐induced CLOCK phosphorylation was abolished by treatment with PKC inhibitors but not by other kinase inhibitors. Consistently, the interaction between CLOCK and PKC was markedly increased shortly after serum shock, and the Ca 2+ ‐dependent PKC isoforms PKCα and PKCγ phosphorylated CLOCK in vitro. Furthermore, phorbol myristic acetate treatment triggered immediate‐early transcription of Per1 and also CLOCK phosphorylation, which were blocked by a Ca 2+ ‐dependent PKC inhibitor. These findings indicate that CLOCK activation through the Ca 2+ ‐dependent PKC pathway might have a substantial role in phase resetting of the circadian clock.