The Role of E-Cadherin, catenin p120ctn, and Hakai in Cell Motility

P120 CAS是一种犰狳型连环蛋白，在3 T3成纤维细胞中诱导细胞过程的显著延伸和细胞运动性的增加。E-钙粘蛋白的p120 CAS结合位点的缺失诱导细胞中类似的运动性增加。小鼠中p120 CAS的基因切除导致在E8.75时发育停滞：纯合突变胚胎不转，并显示有缺陷的脊索，伴随着神经外胚层的戏剧性过度表达。这是一个令人惊讶的表型，需要进一步的工作来阐明p120 CAS在体内细胞运动，细胞粘附和信号传导中的作用。此外，条件基因消融将进行检查的作用，p120 CAS在胚胎发育的后期阶段和成人。我们还发现了新的酪氨酸磷酸化的p120 CAS结合位点的E-cadherin的相互作用伙伴，其中E7，与c-cbl的结构同源的组件。E7可能参与E-cadherin的降解或干扰p120 CAS的功能。E-cadherin与p120 CAS和c-cbl同源物在细胞运动中的相互关系将被检查。

P120CAS is an armadillo-type catenin which in 3T3 fibroblasts induces marked extensions of cellular processes and increased cell motility. Deletion of the p120CAS- binding site of E-cadherin induces similarly increased motility in cells. Gene ablation of p120CAS in the mouse resulted in an arrest of development at E8.75: homozygous mutant embryos do not turn and show a defective notochord, accompanied by dramatic overexpression of the neural ectoderm. This is a surprising phenotype which requires further work to elucidate the role of p120CAS in cell motility, cell adhesion and signalling in vivo. Moreover, conditional gene ablations will be performed to examine the role of p120CAS at later stages of embryogenesis and in the adult. We have also found new interaction partners for the tyrosinephosphorylated p120CAS binding site of E-cadherin, among them E7, a component with structural homology to c-cbl. E7 could play a role in degradation of E-cadherin or interfere with p120CAS function. The interrelationship of E-cadherin with p120CAS and the c-cbl homolog in cell motility will be examined.