PHOSOLAMBAN AND CAM KINASE II IN STOMACH SMOOTH MUSCLE PLASTICITY

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 胃肠平滑肌适应不断变化的条件下的收缩活动。 机械可塑性，如肥大，改变了平滑肌肉的功能能力，以应对 通过重组收缩束来改变需求。细胞内钙离子的波幅和频率 振荡对转化为生理反应的信息进行编码。CaM激酶II具有 钙振荡的分子解码器所需的结构、催化和调节特性。眼底 和结肠平滑肌，它们表现出明显的钙振荡，表达CaM激酶II全酶 特定于组织的酶特性。原位杂交、激酶分析、蛋白印迹和比率计量法 钙成像将被用来研究CaM激酶II如何响应胞浆中的钙瞬变，以便 了解它是如何调节平滑肌收缩活动的。胃肠平滑肥大 与先天性或后天缺陷引起的消化道梗阻所致的肌肉有关 有导致几种运动障碍的病理。细胞体积增加的一部分是由于 血清反应因子调控下收缩蛋白的转录和表达。血清 反应因子是由CaM激酶II磷酸化激活的。胃底和结肠平滑肌表达 含有核定位信号的CaM激酶II剪接变异体。细胞分离，Western blotting， 将使用激酶分析、Q-聚合酶链式反应、磷酸肽图谱和表达蛋白质组学来阐明 CaM激酶II在血清反应因子激活收缩蛋白基因转录中的作用 胃肠道平滑肌肥大在正常生理和疾病中具有重要意义。这个项目将 探讨CaM激酶II在正常激动剂和异常激动剂刺激下的调节及生理作用 胃肠平滑肌肥大。胃肠道酶学特性的测定 平滑肌CaM激酶II与胃肠平滑肌收缩调节的研究 将为开发更好的治疗方法提供更多信息，旨在治疗 引起消化道运动障碍的改变的运动模式的肌源性成分。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Gastrointestinal smooth muscles adapt contractile activities in response to continuously changing conditions. Mechanical plasticity, such as hypertrophy, alters the functional capacity of smooth muscles in response to changing demands by reorganizing contractile bundles. The amplitude and frequency of cytosolic Ca 2+ oscillations encodes information that is translated into physiological responses. CaM kinase II has the structural, catalytic, and regulatory properties required of a molecular decoder of Ca 2+ oscillations. Fundus and colon smooth muscles, which exhibit distinct Ca 2+oscillations, express CaM kinase II holoenzymes with tissue-specific enzymatic properties. In situ hybridization, kinase assays, Western blotting, and ratiometric Ca 2+ imaging will be used to investigate how CaM kinase II responds to cytosolic Ca 2+ transients in order to understand how it modulates smooth muscle contractile activity. Hypertrophy of gastrointestinal smooth muscles due to obstructions of the digestive tract resulting from congenital or acquired defects is associated with pathologies that lead to several motility disorders. Part of the cell volume increase results from elevated transcription and expression of contractile proteins under the control of serum response factor. Serum response factor is activated by CaM kinase II phosphorylation. Fundus and colon smooth muscles express CaM kinase II splice variants containing a nuclear localization signal. Cellular fractionation, Western blotting, kinase assays, Q-PCR, phosphopeptide mapping, and expression proteomics will be used to elucidate the role of CaM kinase II in the activation of contractile protein gene transcription by serum response factor. Gastrointestinal smooth muscle hypertrophy is important in normal physiology and disease. This project will explore the regulation and physiological roles of CaM kinase II in normal agonist-stimulated, and abnormal hypertrophied gastrointestinal smooth muscles. Determining the enzymatic characteristics of gastrointestinal smooth muscle CaM kinase II and investigating the modulation of gastrointestinal smooth muscle contraction by CaM kinase II will provide additional information for developing better therapeutics aimed at treating the myogenic component of the altered motility patterns that underlie digestive tract motility disorders.