title: 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.
authors.affiliation: Department of Pharmacology, School of Medicine, University of California, Irvine, CA 92697, USA.
authors.forename: Satoru
authors.initials: S
authors.lastname: Masubuchi
authors.forename: Tianyan
authors.initials: T
authors.lastname: Gao
authors.forename: Audrey
authors.initials: A
authors.lastname: O'Neill
authors.forename: Kristin
authors.initials: K
authors.lastname: Eckel-Mahan
authors.forename: Alexandra C
authors.initials: AC
authors.lastname: Newton
authors.forename: Paolo
authors.initials: P
authors.lastname: Sassone-Corsi
mesh_terms: D000818:Animals; D002940:Circadian Rhythm / Q000528:radiation effects*; D005786:Gene Expression Regulation / Q000528:radiation effects; D008027:Light; D051379:Mice; D018345:Mice, Knockout; D009687:Nuclear Proteins / Q000172:deficiency / Q000378:metabolism*; D010749:Phosphoprotein Phosphatases / Q000172:deficiency / Q000378:metabolism*; D016875:tau Proteins / Q000378:metabolism
chemical_list: D009687:Nuclear Proteins; D016875:tau Proteins; C519282:PHLPP1 protein, mouse; D010749:Phosphoprotein Phosphatases