Identification of mPer1 phosphorylation sites responsible for the nuclear entry.
Casein kinase 1 epsilon (CK1 epsilon) is an essential component of the circadian clock in mammals and Drosophila. The phosphorylation of Period (Per) proteins by CK1 epsilon is believed to be implicated in their subcellular localization and degradation, but the precise mechanism by which CK1 epsilon affects Per proteins has not been determined. In this study, three putative CK1 epsilon phosphorylation motif clusters in mouse Per1 (mPer1) were identified, and the phosphorylation status of serine and threonine residues in these clusters was examined. Phosphorylation of residues within a region defined by amino acids 653-663 and in particular of Ser-661 and Ser-663, was identified as responsible for the nuclear translocation of mPer1. Furthermore, phosphorylation of these residues may influence the nuclear translocation of a clock protein complex containing mPer1. These findings indicate that mPer1 phosphorylation is a critical aspect of the circadian clock mechanism.
Takano
Atsuko
A
Division of Protein Metabolism, Institute for Protein Research, Osaka University, 3-2 Yamada-Oka, Suita, Osaka 565-0871, Japan. atsuko@protein.osaka-u.ac.jp
Isojima
Yasushi
Y
Nagai
Katsuya
K
D021581:Active Transport, Cell Nucleus; D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D019556:COS Cells; D018797:Cell Cycle Proteins; D002467:Cell Nucleus / Q000378:metabolism*; D002478:Cells, Cultured; D002940:Circadian Rhythm; D003593:Cytoplasm / Q000378:metabolism; D018076:DNA, Complementary / Q000378:metabolism; D005231:Fatty Acids, Unsaturated / Q000494:pharmacology; D005982:Glutathione Transferase / Q000378:metabolism; D015151:Immunoblotting; D051379:Mice; D008856:Microscopy, Fluorescence; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D009687:Nuclear Proteins / Q000737:chemistry / Q000378:metabolism*; D056950:Period Circadian Proteins; D010766:Phosphorylation; D051381:Rats; D011994:Recombinant Proteins / Q000737:chemistry; D012694:Serine / Q000737:chemistry; D013912:Threonine / Q000737:chemistry; D013997:Time Factors; D014162:Transfection
D018797:Cell Cycle Proteins; D018076:DNA, Complementary; D005231:Fatty Acids, Unsaturated; D009687:Nuclear Proteins; C539023:Per1 protein, mouse; C539024:Per1 protein, rat; D056950:Period Circadian Proteins; D011994:Recombinant Proteins; D013912:Threonine; D012694:Serine; D005982:Glutathione Transferase; C038753:leptomycin B