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Proc Natl Acad Sci U S A. 2010 Jan 26;107(4):1642-7. doi: 10.1073/pnas.0910292107. Epub 2010 Jan 4.

Protein phosphatase PHLPP1 controls the light-induced resetting of the circadian clock.

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Department of Pharmacology, School of Medicine, University of California, Irvine, CA 92697, USA.


The pleckstrin homology domain leucine-rich repeat protein phosphatase 1 (PHLPP1) differentially attenuates Akt, PKC, and ERK1/2 signaling, thereby controlling the duration and amplitude of responses evoked by these kinases. PHLPP1 is expressed in the mammalian central clock, the suprachiasmatic nucleus, where it oscillates in a circadian fashion. To explore the role of PHLPP1 in vivo, we have generated mice with a targeted deletion of the PHLPP1 gene. Here we show that PHLPP1-null mice, although displaying normal circadian rhythmicity, have a drastically impaired capacity to stabilize the circadian period after light-induced resetting, producing a large phase shift after light resetting. Our findings reveal that PHLPP1 exerts a previously unappreciated role in circadian control, governing the consolidation of circadian periodicity after resetting.

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