STRUCTURE/FUNCTION ANALYSIS OF K CADHERIN

钙粘附素是一种膜蛋白，介导钙依赖的高亲性 细胞黏附，并已被分为两大类，基于 关于结构上的相似性。I类钙粘附素的原型，E- 钙粘附素在上皮细胞中表达。它下调了监管 与肿瘤转移和侵袭性相关。第II类 钙粘附素包括几乎十个非常密切相关的 缺乏决定高亲性的特定序列的分子 聚合。不仅在以下文件中记录了高级表达式 正常的上皮细胞也可在疏松的组织中，迁移细胞 和肿瘤。因此，H类钙粘附素的功能并不 与I类钙粘附素的功能完全重叠。 这项拟议的研究旨在确定一个人的同亲界面 II类，胎儿肾脏特异性钙粘附素，K-钙粘附素(KCad)，也 被称为钙粘素-6(cadherin-6，cad6)，通过基于 E-和N-钙粘附素的晶体结构。一组变种人将会是 为他们消除同性恋相互作用的能力打分 果蝇S2细胞株。这些数据可以外推到其他 II类亚家族的成员，并可提供分子 钙粘附素功能的药物干预基础。这个 这些突变体的分泌形式抑制肾脏的能力 还将对发展进行评估，这些调查结果将提供 了解潜在分子机制所需的信息 通过间充质发育的其他器官的发育 从上皮到上皮的转变。这种感应相互作用发生在 唾液腺、肺、毛发和牙齿发育。此外， 对细胞黏附在异常生长中的潜在作用的见解 将获得，因为KCad已被记录为上调 在各种肿瘤中，主要是肾癌。

Cadherins are membrane proteins mediating Ca-dependent homophilic cell adhesion and have been categorized into two major groups based on structural similarities. The prototype of class I cadherins, E- cadherin is expressed in epithelial cells. Its downregulation correlates with tumor metastasis and invasiveness. Class II cadherins comprise a list of almost ten very closely related molecules which lack specific sequences determining homophilic aggregation. High level expression has been documented not only in normal epithelial cells but also in loose tissues, migrating cells and neoplasms. Thus the functions of class H cadherins do not completely overlap with functions assigned to class I cadherins. The proposed study aims to identify the homophilic interface of a class II, fetal kidney-specific cadherin, K-cadherin (KCad), also known as cadherin -6 (cad6), by mutational analysis based on the crystal structure of E- and N- cadherin. A panel of mutants will be scored for their ability to abrogate homophilic interactions in the Drosophila S2 cell line. These data can be extrapolated to other members of the class II subfamily and may provide the molecular basis for the pharmacologic intervention of cadherin function. The ability of secreted forms of these mutants to inhibit kidney development will also be evaluated and these findings will provide necessary information to understand molecular mechanisms underlying the development of other organs which develop through mesenchymal- to-epithelial transitions. Such inductive interactions occur during salivary glands, lungs, hair and tooth development. Moreover, insights into potential role for cell adhesion in aberrant growth will be obtained, since KCad has been documented to be upregulated in various neoplasms, mainly kidney carcinoma.