DEVELOPMENTAL FUNCTIONS OF THE P120 CATENIN

连环蛋白具有很高的生物学意义，因为它们结合钙粘蛋白-细胞粘附蛋白的细胞质结构域，形成对组织的形态发生分选和随后的组织身份维持至关重要的复合物。更有趣的是，连环蛋白结合受体酪氨酸激酶、各种肌动蛋白相关蛋白、APC肿瘤抑制因子（在人类结肠癌的进展中最具特征），以及需要与核转录因子直接关联的信号通路成分。我们合作发现，cadherin-catenin复合物含有p120 catenin，它与β -catenin和血小板红蛋白（γ -catenin）具有结构同源性，是src激酶和生长因子受体的首选底物。我们最近的研究已经检查了p120在脊椎动物发育中的作用，并表明p120的功能对适当的细胞迁移至关重要，可能是由于它对钙粘蛋白粘附功能的调节。我们进一步表明，与β -连环蛋白相反，p120不参与Wnt/ β -连环蛋白导向的核信号传导。然而，由于p120最近被发现与POZ/锌指家族的一种新的转录因子Kaiso结合，p120可能调节细胞核中不同的（非wnt / β -catenin）转录事件。本研究旨在探讨Xenopus p120 （Xp120）和Xenopus Kaiso （XKaiso）在早期脊椎动物胚胎发生中的功能。将采用的实验系统是两栖蛙爪蟾，它将提供实验优势，包括从细胞和发育角度评估Xp120和XKaiso的功能。目标：1；Xp120与钙粘蛋白相关的发育功能是什么？2. XKaiso的发育功能是什么，在多大程度上通过Xp120调控？

The catenin proteins are of high biological interest given that they bind the cytoplasmic domains of cadherin cell-cell adhesion proteins, forming a complex essential to the morphogenic sorting of tissues and the subsequent maintenance of tissue identities. Of additional intrigue, catenins bind receptor tyrosine kinases, various actin-associated proteins, the APC tumor suppressor (best characterized in the progression of human colon cancer), and components of signaling pathways that require their direct association with nuclear transcription factors. We have collaboratively revealed that the cadherin-catenin complex contains the p120 catenin, which bears structural homology with both beta-catenin and plakoglobin (gamma-catenin), and is a preferred substrate of src kinase and growth factor receptors. Our recent studies have examined the role of p120 in vertebrate development, and indicate that p120 function is critical for proper cell migration, likely resulting from its modulation of cadherin adhesive function. We have further shown that in contrast to beta-catenin, p120 does not engage in Wnt/ beta-catenin-directed nuclear signaling. However, since p120 was recently revealed to bind a novel transcription factor, Kaiso, of the POZ/zinc-finger family, p120 is likely to modulate distinct (non-Wnt/beta-catenin) transcriptional events in the nucleus. This proposal aims to discern the functions of Xenopus p120 (Xp120) and Xenopus Kaiso (XKaiso) in early vertebrate embryogenesis. The experimental system to be employed is the amphibious frog Xenopus, which will offer experimental advantages including the capacity to functionally evaluate Xp120 and XKaiso from both cellular and developmental perspectives. Aims Addressed: 1. What are the developmental functions of Xp120 in association with Cadherins? 2. What are the developmental functions of XKaiso, and to what extent are they modulated via Xp120?