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タイトル: CK1δ/ε protein kinase primes the PER2 circadian phosphoswitch
著者: Narasimamurthy, Rajesh
Hunt, R., Sabrina
Lu, Yining
Fustin, Jean-Michel  kyouindb  KAKEN_id
Okamura, Hitoshi
Partch, L., Carrie
Forger, B., Daniel
Kim, Kyoung, Jae
Virshup, M., David
著者名の別形: 岡村, 均
キーワード: circadian rhythms
protein kinase
cell regulation
発行日: 16-May-2018
出版者: National Academy of Sciences
誌名: National Academy of Sciences
論文番号: 201721076
抄録: Multisite phosphorylation of the PERIOD 2 (PER2) protein is the key step that determines the period of the mammalian circadian clock. Previous studies concluded that an unidentified kinase is required to prime PER2 for subsequent phosphorylation by casein kinase 1 (CK1), an essential clock component that is conserved from algae to humans. These subsequent phosphorylations stabilize PER2, delay its degradation, and lengthen the period of the circadian clock. Here, we perform a comprehensive biochemical and biophysical analysis of mouse PER2 (mPER2) priming phosphorylation and demonstrate, surprisingly, that CK1δ/ε is indeed the priming kinase. We find that both CK1ε and a recently characterized CK1δ2 splice variant more efficiently prime mPER2 for downstream phosphorylation in cells than the well-studied splice variant CK1δ1. While CK1 phosphorylation of PER2 was previously shown to be robust to changes in the cellular environment, our phosphoswitch mathematical model of circadian rhythms shows that the CK1 carboxyl-terminal tail can allow the period of the clock to be sensitive to cellular signaling. These studies implicate the extreme carboxyl terminus of CK1 as a key regulator of circadian timing.
著作権等: © 2018 the Author(s). Published by PNAS. This open access article is distributed under Creative Commons Attribution-NonCommercial-NoDerivatives License 4.0 (CC BY-NC-ND).
URI: http://hdl.handle.net/2433/231232
DOI(出版社版): 10.1073/pnas.1721076115
PubMed ID: 29784789
出現コレクション:学術雑誌掲載論文等

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