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）： 我的长期目标是在医学领域实现学术生涯，继续教学，并在胃肠道信号转导领域建立独立的研究项目。同时，我希望继续从事临床医学实践，最终为与健康相关的基础研究的进步做出贡献。特别是，虽然我的工作分析细胞信号传导的分子机制，但我的目标是研究这些发育过程，例如肠道生长和成熟，或对成人和儿童群体重要的问题，例如炎症性肠病。 我更紧迫的首要任务是获得拨款支持，以便继续我的研究和作为一名科学家的成长。我为我最初的初级教职职位寻找一个环境，既能为我提供刺激科学发展的深度资源，又能为我提供受保护的研究时间的坚定承诺。我选择了加州大学洛杉矶分校和我的导师 Enrique Rozengurt 博士，因为他在信号转导领域的专业知识、大学的资源以及 Rozengurt 博士和儿科部门对支持我的培训的承诺。 该研究计划的重点是了解环境信号转化为肠上皮细胞功能的机制。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伤口恢复的模型。具体来说，我们的目标是研究 G 蛋白偶联受体 (GPCR) 激动剂反应中的信号通路。我们要讨论的中心假设是细胞质酪氨酸激酶 Pyk2 负责整合肠上皮细胞中的多种信号，并在介导其细胞效应中发挥关键作用。我们的第一个具体目标是研究在刺激 GPCR 信号后，Pyk2 通过不同位点的磷酸化以及与其他信号蛋白的相互作用进行的调节。我们的第二个目标是将 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 合成和细胞运动中的作用。通过阐明肠上皮中的关键信号转导途径，我们将更好地了解胃肠道上皮生长、伤口愈合和肿瘤形成过程的潜在机制。