COBRE: UNV MED SCH: P2: CAM KINASE II IN SMOOTH MUSCLE PLASTICITY

该子项目是利用NIH/NCRR资助的中心赠款提供的资源的许多研究子项目之一。子项目和研究者（PI）可能从另一个NIH来源获得了主要资金，因此可以在其他CRISP条目中表示。所列机构为中心机构，不一定是研究者机构。胃肠平滑肌适应收缩活动，以应对不断变化的条件。机械可塑性，如肥大，通过重组收缩束改变平滑肌的功能能力，以响应不断变化的需求。胞质内Ca 2+振荡的幅度和频率编码信息，这些信息被转化为生理反应. CaM激酶II具有Ca 2+振荡分子解码器所需的结构、催化和调节特性。胃底和结肠平滑肌，表现出不同的钙振荡，表达钙调蛋白激酶II全酶与组织特异性的酶的性质。原位杂交、激酶测定、蛋白质印迹和比率Ca 2 <$$>成像将用于研究CaM激酶II如何响应胞质Ca 2 <$瞬态，以了解其如何调节平滑肌收缩活性。由于先天性或后天性缺陷引起的消化道阻塞导致的胃肠平滑肌肥大与导致几种动力障碍的病理学有关。细胞体积的增加部分是由于在血清反应因子的控制下收缩蛋白的转录和表达升高所致。血清反应因子通过CaM激酶II磷酸化激活。胃底和结肠平滑肌表达含有核定位信号的CaM激酶II剪接变体。细胞分级分离，蛋白质印迹，激酶测定，Q-PCR，磷酸肽图谱，和表达蛋白质组学将被用来阐明的作用，钙调蛋白激酶II的收缩蛋白基因转录激活的血清反应因子。胃肠平滑肌肥大在正常生理和疾病中是重要的。本研究将探讨钙调素激酶II在正常激动剂刺激及异常肥大的胃肠平滑肌中的调节及生理作用。确定胃肠道平滑肌钙调素激酶II的酶特性和调查的调制胃肠道平滑肌收缩钙调素激酶II将提供更多的信息，开发更好的治疗，旨在治疗肌源性成分的改变动力模式的基础消化道动力障碍。

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.