Casein kinase I: another cog in the circadian clockworks.
Multiple components of the circadian central clock are phosphoproteins, and it has become increasingly clear that posttranslational modification is an important regulator of circadian rhythm in diverse organisms, from dinoflagellates to humans. Genetic studies in Drosophila have identified double-time (dbt), a serine/threonine protein kinase that is highly homologous to human casein kinase I epsilon (CKIepsilon), as the first kinase linked to behavioral rhythms. Identification of a missense mutation in CKIepsilon as the tau mutation in the Syrian hamster places CKIepsilon within the core clock machinery in mammals. Most recently, identification of a phosphorylation site mutant of hPER2 in a family with an inherited circadian rhythm abnormality strongly suggests that PER2 is a physiologically relevant substrate of CKI. Phosphorylation may regulate multiple properties of clock proteins, including stability and intracellular localization.
Eide
E J
EJ
Department of Oncological Sciences and the Center for Children, Huntsman Cancer Institute, University of Utah, Salt Lake City 84112, USA.
Virshup
D M
DM
D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D048149:Casein Kinase 1 epsilon; D047388:Casein Kinases; D002940:Circadian Rhythm; D006224:Cricetinae; D004330:Drosophila; D029721:Drosophila Proteins; D008647:Mesocricetus; D008969:Molecular Sequence Data; D009154:Mutation; D020125:Mutation, Missense; D010766:Phosphorylation; D011494:Protein Kinases / Q000235:genetics / Q000378:metabolism* / Q000502:physiology*; D017386:Sequence Homology, Amino Acid
D029721:Drosophila Proteins; C113519:dco protein, Drosophila; D011494:Protein Kinases; D048149:Casein Kinase 1 epsilon; D047388:Casein Kinases