Wildenberg Gregg A, Dohn Michael R, Carnahan Robert H, Davis Michael A, Lobdell Nichole A, Settleman Jeffrey, Reynolds Albert B
Department of Cancer Biology, 438 Preston Building, Vanderbilt University, Nashville, TN 37232, USA.
Cell. 2006 Dec 1;127(5):1027-39. doi: 10.1016/j.cell.2006.09.046.
Integration of receptor tyrosine kinase, integrin, and cadherin activities is crucial for normal cell growth, motility, and adhesion. Here, we describe roles for p120-catenin (p120) and p190RhoGAP that coordinate crosstalk between these systems and regulate cadherin function. Surprisingly, PDGFR-induced actin remodeling in NIH3T3 cells is blocked in the absence of p120, and the cells are partially transformed via constitutive activation of Rho. We have traced the mechanism to unexpected codependent roles for p120 and p190RhoGAP in regulating Rac-dependent antagonism of Rho. Receptor-induced Rac activity causes translocation of p190RhoGAP to adherens junctions (AJs), where it couples to the cadherin complex via interaction with p120. AJ formation is dependent on this p120-p190RhoGAP interaction and fails altogether if either of these proteins are compromised. We propose that Rac activation links diverse signaling systems to AJ assembly by controlling transient p190RhoGAP interactions with p120 and localized inhibition of Rho.
受体酪氨酸激酶、整合素和钙黏蛋白活性的整合对于正常细胞生长、运动和黏附至关重要。在此，我们描述了p120连环蛋白（p120）和p190RhoGAP的作用，它们协调这些系统之间的串扰并调节钙黏蛋白功能。令人惊讶的是，在缺乏p120的情况下，PDGFR诱导的NIH3T3细胞中的肌动蛋白重塑被阻断，并且细胞通过Rho的组成型激活而部分转化。我们已将该机制追溯到p120和p190RhoGAP在调节Rho的Rac依赖性拮抗作用中意想不到的共依赖作用。受体诱导的Rac活性导致p190RhoGAP易位至黏附连接（AJs），在那里它通过与p120相互作用而与钙黏蛋白复合物结合。AJ的形成依赖于这种p120 - p190RhoGAP相互作用，如果这两种蛋白质中的任何一种受损则完全无法形成。我们提出，Rac激活通过控制p190RhoGAP与p120的瞬时相互作用以及对Rho的局部抑制，将多种信号系统与AJ组装联系起来。
