DEVELOPMENTAL FUNCTIONS OF THE P120 CATENIN

连接素蛋白具有很高的生物学价值，因为它们结合了钙粘蛋白细胞-细胞黏附蛋白的细胞质结构域，形成了一种对组织的形态发生分类和随后的组织特性维持必不可少的复合体。更有趣的是，连环蛋白结合了受体酪氨酸激酶、各种肌动蛋白相关蛋白、APC肿瘤抑制因子(最适合于人类结肠癌的进展)，以及需要它们与核转录因子直接关联的信号通路组件。我们合作发现，钙粘素-连环蛋白复合体包含p120连环蛋白，它与β-连环蛋白和蛋白球蛋白(伽马-连环蛋白)具有结构上的同源性，是src激酶和生长因子受体的首选底物。我们最近的研究考察了p120在脊椎动物发育中的作用，并表明p120功能是细胞正常迁移的关键，可能是由于其对钙粘附素黏附功能的调节。我们进一步证明，与β-连环素相反，p120不参与Wnt/β-连环素导向的核信号。然而，由于p120最近被发现与POZ/锌指家族的一个新的转录因子Kaiso结合，p120很可能在细胞核中调节不同的(非Wnt/β-catenin)转录事件。本研究旨在探讨非洲爪哇p120(Xp120)和非洲爪哇Kaiso(XKaiso)在脊椎动物早期胚胎发育中的作用。将使用的实验系统是两栖青蛙非洲爪蛙，它将提供实验优势，包括从细胞和发育角度对Xp120和XKaiso进行功能评估的能力。目标：1.Xp120与钙粘素相关的发育功能是什么？2.XKaiso的发育功能是什么？Xp120在多大程度上调节了它们？

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?