MINORITY PREDOCTORAL FELLOWSHIP PROGRAM

少数族裔博士前奖学金计划

• 批准号: 7230750
• 负责人: Mark W Schramp
• 金额: $ 3万
• 依托单位: UNIVERSITY OF CALIFORNIA BERKELEY
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-03-14 至 2009-03-13
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7230750
• 关键词: actins; human; lead; neoplasm /cancer; phenotype; phosphorylation; play; polymerization; proteins; role; tyrosine; vinculin

DESCRIPTION (provided by applicant): The long term goal of this project is to understand how Src can induce the formation of podosomes leading to an invasive phenotype. Many human cancers have elevated Src kinase activity, and tumor progression, especially metastatic tumors, correlates with this increase in activity. Increased Src activity constitutively stimulates many downstream signaling pathways leading to the formation of invasive structures termed podosomes. Podosomes are sites of actin polymerization, cell attachment and protease secretion. Many proteins associated with these processes are direct Src substrates. We hope to gain insight into what proteins and signaling pathways are essential for podosome formation and cellular invasion. To do this, we are going to utilize RNAi technology to knockout the integrin-F-actin linker protein and Src substrate vinculin. We can then test how Src phosphorylation of vinculin effects its overall function in vivo. Second, we are going to look at the role of ERK5 in podosome formation and invasion. Preliminary data from our lab indicate that ERK5 activity is required for podosome formation. Using ERK5 -/- cells we will express an activated form of Src and determine its capacity to induce podosome formation.

描述（由申请人提供）：该项目的长期目标是了解 Src 如何诱导足体的形成，从而导致侵袭性表型。许多人类癌症的 Src 激酶活性升高，肿瘤进展，尤其是转移性肿瘤，与这种活性的增加相关。 Src 活性的增加会持续刺激许多下游信号通路，从而导致称为足小体的侵入性结构的形成。足体是肌动蛋白聚合、细胞附着和蛋白酶分泌的位点。许多与这些过程相关的蛋白质都是直接 Src 底物。我们希望深入了解哪些蛋白质和信号通路对于足体形成和细胞侵袭至关重要。为此，我们将利用 RNAi 技术敲除整合素-F-肌动蛋白连接蛋白和 Src 底物纽蛋白。然后我们可以测试纽蛋白的 Src 磷酸化如何影响其体内的整体功能。其次，我们将研究 ERK5 在足体形成和侵袭中的作用。我们实验室的初步数据表明 ERK5 活性是足小体形成所必需的。使用 ERK5 -/- 细胞，我们将表达 Src 的激活形式并确定其诱导足小体形成的能力。