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

P120CAS是一种犰狳型连环蛋白，在3T3成纤维细胞中诱导细胞过程的显著延长和细胞运动性的增加。E-cadherin的p120CAS结合位点的缺失同样会引起细胞运动性的增加。小鼠p120CAS基因切除导致发育在E8.75处停止：纯合突变胚胎不转，显示有缺陷的脊索，并伴有神经外胚层的过度表达。这是一个令人惊讶的表型，需要进一步的工作来阐明p120CAS在细胞运动、细胞粘附和体内信号传导中的作用。此外，将进行有条件的基因消融，以检查p120CAS在胚胎发生后期和成人中的作用。我们还发现了E-cadherin酪氨酸磷酸化的p120CAS结合位点的新的相互作用伙伴，其中包括与c-cbl结构同源的成分E7。E7可能参与E-cadherin的降解或干扰p120CAS的功能。E-cadherin与p120CAS和c-cbl同源物在细胞运动中的相互关系将被研究。

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.