Pyk2 Signaling In Intestinal Epithelial Cells

肠上皮细胞中的 Pyk2 信号转导

• 批准号: 6719102
• 负责人: STEVEN S WU
• 金额: $ 12.18万
• 依托单位: UNIVERSITY OF CALIFORNIA LOS ANGELES
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-03-15 至 2005-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6719102
• 关键词: Pyk2; Signaling; Intestinal; Epithelial; Cells

DESCRIPTION (provided by applicant): My long-term goal is to achieve an academic career in medicine, continue to teach, and to establish an independent program of research in the field of gastrointestinal signal transduction. At the same time, I wish to continue in the practice of clinical medicine, and ultimately to contribute to the advancement of basic research as it relates to health. In particular, though my work analyzes molecular mechanisms of cell signaling, I aim to study these with an eye towards developmental processes, such as intestinal growth and maturation, or towards issues important to both adult and child populations, such as inflammatory bowel disease. My more immediate priority is to obtain grant support in order to continue both my research and my growth as a scientist. I seek an environment for my initial junior faculty position that will provide me with both a depth of resources to stimulate scientific growth, and a strong commitment to protected research time. I have chosen UCLA and my mentor, Dr. Enrique Rozengurt, because of his expertise in the field of signal transduction, the resources of the university, and the commitment of Dr. Rozengurt and of the Department of Pediatrics to support my training. This research proposal focuses on understanding the mechanisms by which environmental signals are translated into cellular functions in intestinal epithelia. Intestinal epithelial cell functions, including growth, migration, and differentiation, are regulated by a wide variety of soluble and contact-dependent stimuli. The IEC-6 and IEC-18 small intestinal epithelial cell lines have been widely used as models of proliferation and wound restitution. Specifically, we aim to study signaling pathways in the response to G protein-coupled receptor (GPCR) agonists. The central hypothesis we will address is that the cytoplasmic tyrosine kinase Pyk2 acts to integrate multiple signals in intestinal epithelial cells and plays a key role in mediating their cellular effects. Our first specific aim is to study the regulation of Pyk2 by phosphorylation at distinct sites, and by interactions with other signaling proteins, following stimulation of GPCR signaling. Our second aim is to correlate Pyk2 activity to cytoskeletal structure and function. The third aim is to evaluate the role of Pyk2 in regulating DNA synthesis and cell motility. By elucidating key signal transduction pathways in the intestinal epithelium, we will better understand the mechanisms underlying the processes of growth, wound healing, and neoplasia in the GI epithelium.

描述（由申请人提供）： 我的长期目标是实现医学学术职业，继续教书，并在胃肠道信号转导领域建立独立的研究计划。同时，我希望继续进行临床医学实践，并最终为与健康有关的基础研究的发展做出贡献。特别是，尽管我的工作分析了细胞信号传导的分子机制，但我的目的是注重发育过程，例如肠道生长和成熟，或者对对成人和儿童种群（例如炎症性肠病）重要的问题进行研究。 我更直接的优先事项是获得赠款支持，以继续我的研究和作为科学家的成长。我为初级教师职位寻求环境，这将为我提供刺激科学增长的深度，又是对受保护的研究时间的坚定承诺。我之所以选择加州大学洛杉矶分校和我的导师恩里克·罗Zengurt（Enrique Rozengurt）博士，是因为他在信号转导，大学的资源以及罗Zengurt博士的承诺和儿科部的承诺方面的承诺来支持我的培训。 该研究建议着重于理解环境信号转化为肠上皮中细胞功能的机制。肠上皮细胞功能，包括生长，迁移和分化，受到多种可溶性和接触依赖性刺激的调节。 IEC-6和IEC-18小肠上皮细胞系已被广泛用作增殖和恢复伤口的模型。具体而言，我们旨在研究对G蛋白偶联受体（GPCR）激动剂的反应中的信号通路。我们将要解决的中心假设是，细胞质酪氨酸激酶PYK2起着在肠上皮细胞中整合多个信号，并在介导其细胞效应中起关键作用。我们的第一个具体目的是在刺激GPCR信号传导后，通过不同位点的磷酸化研究PYK2的调节，以及与其他信号蛋白的相互作用。我们的第二个目的是将PYK2活性与细胞骨架结构和功能相关联。第三个目的是评估PYK2在调节DNA合成和细胞运动性中的作用。通过阐明肠上皮中的钥匙信号转导途径，我们将更好地了解GI上皮中生长，伤口愈合和肿瘤过程的基础机制。