CK1 and GSK3 in the Drosophila and Mammalian Circadian Clock
Abstract
Two kinases, DOUBLETIME and SHAGGY, have been shown to play a role in the circadian clock. DOUBLETIME, the Drosophila orthologue of casein kinase 1, can phosphorylate PERIOD in the cytoplasm and in the nucleus. This phosphorylation destabilizes PERIOD in both locations and sets patterns of both cytoplasmic accumulation and nuclear turnover. Cytoplasmic phosphorylation postpones accumulation of PERIOD and affects timing of nuclear accumulation of PERIOD/ TIMELESS complexes. SHAGGY, the Drosophila orthologue of glycogen synthase kinase 3, phosphorylates TIMELESS and promotes nuclear translocation of PERIOD/ TIMELESS complexes. Thus, the opposing effects of these two kinases in the cytoplasm are crucial for establishing the approximately 24 h period of circadian rhythmicity in Drosophila. Casein Kinase 1 has been shown to be a component of the circadian clock in mammals. Recent studies are also pointing to a role for glycogen synthase kinase 3 in the mammalian clock.
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PER and CRY proteins are phosphorylated by Casein Kinase I ε and δ and Glycogen Synthase Kinase 3β, leading to changes in their stability, association, and nuclear entry.
“The PER and CRY proteins are translated in the cytoplasm, and are phosphorylated by Casein Kinase I ε and δ (CK1) and Glycogen Synthase Kinase 3β (GSK3β), leading to changes in their stability, association, and nuclear entry (Harms et al., 2003; Iitaka et al., 2005; Knippschild et al., 2005; Kurabayashi et al., 2006).”
From Circadian genes, rhythms and the biology of mood disorders (2007) · cites this paper as Harms et al., 2003
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“The PER and CRY proteins are translated in the cytoplasm, and are phosphorylated by Casein Kinase I ε and δ (CK1) and Glycogen Synthase Kinase 3β (GSK3β), leading to changes in their stability, association, and nuclear entry (Harms et al., 2003;Iitaka et al., 2005;Knippschild et al., 2005;Kurabayashi et al., 2006).”
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Protein Phosphatase 4 ist ein neuer Regulator der circadianen Uhr in Säugern
Mathematisch-naturwissenschaftlichen Fakultät, I. (2014)
- Authors
- Harms, E., Young, M. W., & Saez, L.
- Affiliations
- Rockefeller University (US)
- ORCID
- Young, Michael W.
- Venue
- Novartis Foundation Symposia
- Publisher
- Wiley
- Published
- 2003-10-28
- Volume
- 253
- Pages
- 267-280
- ISSN
- 1528-2511 (ISSN-L)
- 1935-4657
- OpenAlex
- W1521928376
- Cited by
- 27
- References
- 0
- Citations by year
- 2018: 2 · 2014: 4 · 2012: 3
- Type
- other
- Language
- en
- Open access
- closed
- Locations
- Novartis Foundation symposium (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute of General Medical Sciences (GM-54339)
- Topics
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Circadian rhythm and melatonin
- Physical Sciences › Physics and Astronomy › Atomic and Molecular Physics, and Optics › Advanced Frequency and Time Standards
- Life Sciences › Agricultural and Biological Sciences › Plant Science › Plant Molecular Biology Research
- Keywords
- circadian clock, casein kinase 1, glycogen synthase kinase-3, Shaggy, PERIOD protein, protein phosphorylation, protein degradation, nuclear translocation, Drosophila, mammalian circadian clock
- MeSH terms
- Amino Acid Sequence, Animals, Circadian Rhythm, Drosophila, Mammals, Molecular Sequence Data, Mutation, Phosphorylation, Protein Kinases, Genes, Insect, Glycogen Synthase Kinase 3, Casein Kinases
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