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

ABSTRACT: 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.

SUBMITTER: Masubuchi S

PROVIDER: S-EPMC2824391 | biostudies-literature | 2010 Jan

REPOSITORIES: biostudies-literature

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

Masubuchi Satoru S Gao Tianyan T O'Neill Audrey A Eckel-Mahan Kristin K Newton Alexandra C AC Sassone-Corsi Paolo P

Proceedings of the National Academy of Sciences of the United States of America 20100104 4

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, althoug ...[more]

PMID: 20080691

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