CONTROL OF EPITHELIAL CELL MOTILITY BY E CADHERIN

E 钙粘蛋白对上皮细胞运动的控制

• 批准号: 2899921
• 负责人: ROBERT W BRACKENBURY
• 金额: $ 22.58万
• 依托单位: UNIVERSITY OF CINCINNATI
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-04-10 至 2002-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2899921
• 关键词: MDCK cell; cadherins; cell motility; epithelium; genetically modified animals; keratinocyte; laboratory mouse; mammary epithelium; phosphorylation; protein structure function; wound healing; yeast two hybrid system

DESCRIPTION: (Adapted from the applicant's abstract) - The hypothesis of this revised application is that epithelial cell motility is suppressed by signals generated as a result of E-cadherin mediated cell-cell contact. Published findings from the principal investigator's lab have shown that the catenin binding domain of E-cadherin is required for adhesion, but not for suppression of motility, whereas the JM domain (comprising 30-50 amino acids just next the to plasma membrane) suppresses motility but does not support adhesion in many cell types. Data from a new collaborator, Michael Kinch, indicate that engagement of E-cadherin stimulates the tyrosine phosphorylation of several proteins in breast epithelial cells and MDCK cells. A new specific aim (Aim 1) based on these data is to determine whether this is the case for keratinocytes as well and then determine which parts of the E-cad tail are required to generate this tyrosine phosphorylation response and identify tyrosine-phosphorylated proteins. Aim 2 proposes to identify components that interact with the JM domain of E-cadherin and test their role in suppression of motility. The final aim is to determine the role of the JM domain in regulating the motility of keratinocytes in vitro and in vivo. This will be accomplished first by expressing dominant-negative forms of E-cadherin and N-cadherin in cultured cells, and then using the K14 promoter to target selected dominant-negative constructs to the epidermis of transgenic mice.

描述：（根据申请人的摘要改编） - 修订后的应用是上皮细胞运动被抑制 E-钙粘着蛋白介导的细胞 - 细胞接触产生的信号。 主要研究者实验室的发表发现表明 粘附需要E-钙粘着蛋白的链氨酸结合结构域，但不需要 抑制运动性，而JM结构域（包括30-50个氨基酸 接下来，到质膜）抑制运动性，但不支持 许多细胞类型的粘附。 来自新合作者迈克尔·金奇（Michael Kinch）的数据 表明e-钙粘蛋白的互动会刺激酪氨酸 乳腺上皮细胞和MDCK中几种蛋白质的磷酸化 细胞。 基于这些数据的新特定目标（AIM 1）是确定 角质形成细胞是否也是如此 需要E-CAD尾巴的一部分来产生这种酪氨酸 磷酸化反应并鉴定酪氨酸磷酸化蛋白。 目的 2提出确定与JM域相互作用的组件 电子 - 钙粘蛋白并测试其在抑制运动性中的作用。 最终目标是 确定JM域在调节运动中的作用 体外和体内角质形成细胞。 这将首先通过 在培养中表达E-钙粘蛋白和N-钙粘着蛋白的显性阴性形式 细胞，然后使用K14启动子靶向选定的主要阴性 构造转基因小鼠表皮。