Discovery of MARK2 as a physiological kinase for PER2 in the mammalian clock - PubMed
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- #circadian clock
- #PER2
- #MARK2
- Discovery of MARK2 as a physiological kinase for PER2 in the mammalian circadian clock.
- Human mutation in serine 662 (S662) linked to familial advanced sleep phase (FASP) syndrome.
- S662 phosphorylation by multiple kinases (CK1δ/ε, TSSK1/2, SIK1-3) but no circadian phenotype from their deletion.
- Biochemical purification identified MARK2 as the kinase phosphorylating S662, binding to and stabilizing PER2.
- Mark2-deficient cells showed shortened circadian period dependent on S662.
- Neuronal-specific Mark2 knockout mice exhibited phase advancement and period shortening.
- Demonstrated effectiveness of biochemical purification in studying behavioral mechanisms.