Rapid activation of CLOCK by Ca2+-dependent protein kinase C mediates resetting of the mammalian circadian clock

Hong Seok Shim, Hyunjung Kim, Jiwon Lee, Gi Hoon Son, Sehyung Cho, Tae H. Oh, Sang Hyeon Kang, Dong Seung Seen, Kun Ho Lee, Kyungjin Kim

Research output: Contribution to journalArticle

53 Citations (Scopus)

Abstract

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 Ca2+-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 Ca2+-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 Ca2+-dependent PKC inhibitor. These findings indicate that CLOCK activation through the Ca2+-dependent PKC pathway might have a substantial role in phase resetting of the circadian clock.

Original languageEnglish
Pages (from-to)366-371
Number of pages6
JournalEMBO Reports
Volume8
Issue number4
DOIs
Publication statusPublished - 2007 Apr 1
Externally publishedYes

Fingerprint

Circadian Clocks
Protein Kinase C
Clocks
Chemical activation
Phosphorylation
Transcription
Protein C Inhibitor
Protein Kinase Inhibitors
Serum
CLOCK Proteins
Mammals
Fibroblasts
Shock
Protein Isoforms
Acetates
Phosphotransferases
Genes
Molecules

ASJC Scopus subject areas

  • Genetics
  • Cell Biology

Cite this

Rapid activation of CLOCK by Ca2+-dependent protein kinase C mediates resetting of the mammalian circadian clock. / Shim, Hong Seok; Kim, Hyunjung; Lee, Jiwon; Son, Gi Hoon; Cho, Sehyung; Oh, Tae H.; Kang, Sang Hyeon; Seen, Dong Seung; Lee, Kun Ho; Kim, Kyungjin.

In: EMBO Reports, Vol. 8, No. 4, 01.04.2007, p. 366-371.

Research output: Contribution to journalArticle

Shim, HS, Kim, H, Lee, J, Son, GH, Cho, S, Oh, TH, Kang, SH, Seen, DS, Lee, KH & Kim, K 2007, 'Rapid activation of CLOCK by Ca2+-dependent protein kinase C mediates resetting of the mammalian circadian clock', EMBO Reports, vol. 8, no. 4, pp. 366-371. https://doi.org/10.1038/sj.embor.7400920
Shim, Hong Seok ; Kim, Hyunjung ; Lee, Jiwon ; Son, Gi Hoon ; Cho, Sehyung ; Oh, Tae H. ; Kang, Sang Hyeon ; Seen, Dong Seung ; Lee, Kun Ho ; Kim, Kyungjin. / Rapid activation of CLOCK by Ca2+-dependent protein kinase C mediates resetting of the mammalian circadian clock. In: EMBO Reports. 2007 ; Vol. 8, No. 4. pp. 366-371.
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