Protein phosphatase PHLPP1 controls the light-induced resetting of the circadian clock
Protein phosphatase PHLPP1 controls the light-induced resetting of the circadian clock
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DOI：
10.1073/pnas.0910292107
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发表时间：
2010-01-26
影响因子：
11.1
通讯作者：
Sassone-Corsi, Paolo
中科院分区：
文献类型：
--
作者：
Masubuchi, Satoru;Gao, Tianyan;Sassone-Corsi, Paolo
普列克底物蛋白同源结构域富亮氨酸重复蛋白磷酸酶1（PHLPP 1）差异性地减弱Akt、PKC和ERK 1/2信号传导，从而控制由这些激酶引起的反应的持续时间和幅度。PHLPP 1在哺乳动物的中枢时钟-视交叉上核中表达，在那里它以昼夜节律的方式振荡。为了探索PHLPP 1在体内的作用，我们已经产生了PHLPP 1基因靶向缺失的小鼠。在这里，我们表明，PHLPP 1-null小鼠，虽然显示正常的昼夜节律，有一个严重受损的能力，以稳定光诱导复位后的昼夜节律周期，产生一个大的相移后，光复位。我们的研究结果表明，PHLPP 1发挥了以前不受重视的作用，在昼夜节律控制，管理的巩固后重置的昼夜节律周期。
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.