ERK/MAPK Signaling and Circadian Clock Entrainment

ERK/MAPK 信号传导和昼夜节律时钟夹带

• 批准号: 6885576
• 负责人: GREGORY Q BUTCHER
• 金额: $ 3.19万
• 依托单位: OHIO STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-09-30 至 2007-09-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6885576
• 关键词: antisense nucleic acid; biological signal transduction; cAMP response element binding protein; circadian rhythms; enzyme activity; gene environment interaction; gene expression; genetic transcription; genetically modified animals; glutamates; laboratory mouse; messenger RNA; mitogen activated protein kinase; oligonucleotides; polymerase chain reaction; predoctoral investigator; suprachiasmatic nucleus; tissue /cell culture; transfection

DESCRIPTION (provided by applicant): The endogenous pacemaker located in the mammalian suprachiasmatic nucleus (SCN) maintains 24 hr periodicity over an array of biochemical, physiological and behavioral processes. The inherent timing mechanism of the SCN is entrained by external time cues, of which light is the most potent. Recent evidence has indicated the p42/44 mitogen activated protein kinase (MAPK) signaling pathway couples light to clock entrainment. As an initial characterization of how MAPK signaling affects the clock, I have compiled data indicating that members of the p90 ribosomal S6 kinase (RSK) and mitogen and stress activated kinase (MSK) families function as MAPK-regulated kinases in the SCN. Given the roles of these kinases in transcriptional regulation, I hypothesize that RSKs and MSKs couple light to gene expression and, in turn, entrainment of the mammalian circadian clock. The specific aims of this proposal are to 1) determine the contribution of ERK and its downstream targets MSKs and RSKs to the expression of light-activated, circadian clock-regulated, genes, and 2) test the hypothesis that MSKs and RSKs couple light to entrainment of the circadian clock. A combination of cellular, molecular and behavioral assays will be used.

描述（由申请人提供）：位于哺乳动物上核核（SCN）中的内源性起搏器（SCN）在一系列生化，生理和行为过程中保持24小时的周期性。 SCN的固有定时机制是由外部时间提示所包围的，其中最有效的光线是最有效的。最近的证据表明，p42/44有丝分裂原激活的蛋白激酶（MAPK）信号通路伴侣将光线与时钟夹带。作为MAPK信号如何影响时钟的初始表征，我编制了数据，表明P90核糖体S6激酶（RSK）的成员和有丝分裂原和胁迫激活的激酶（MSK）家族在SCN中充当MAPK调节的激酶。鉴于这些激酶在转录调控中的作用，我假设RSK和MSK将夫妇发光到基因表达，然后又夹住了哺乳动物昼夜节律时钟。该提案的具体目的是对1）确定ERK及其下游目标对MSK和RSK的贡献对光激活，昼夜节律时钟调节，基因和2）测试MSK和RSK对昼夜节律夹带的假设进行的假设。将使用细胞，分子和行为测定的组合。