TY - JOUR
T1 - Protein phosphatase PHLPP1 controls the light-induced resetting of the circadian clock
AU - Masubuchi, Satoru
AU - Gao, Tianyan
AU - O'Neill, Audrey
AU - Eckel-Mahan, Kristin
AU - Newton, Alexandra C.
AU - Sassone-Corsi, Paolo
PY - 2010/1/26
Y1 - 2010/1/26
N2 - 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. Hereweshowthat 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.
AB - 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. Hereweshowthat 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.
KW - After-effect
KW - Per
KW - Period
KW - Phase shift
KW - Suprachiasmatic nucleus
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U2 - 10.1073/pnas.0910292107
DO - 10.1073/pnas.0910292107
M3 - Article
C2 - 20080691
AN - SCOPUS:76549120525
SN - 0027-8424
VL - 107
SP - 1642
EP - 1647
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
IS - 4
ER -