%0 Journal Article
%T Regulation of Adherens Junction Dynamics by Phosphorylation Switches
%A Cristina Bertocchi
%A Megha Vaman Rao
%A Ronen Zaidel-Bar
%J Journal of Signal Transduction
%D 2012
%I Hindawi Publishing Corporation
%R 10.1155/2012/125295
%X Adherens junctions connect the actin cytoskeleton of neighboring cells through transmembrane cadherin receptors and a network of adaptor proteins. The interactions between these adaptors and cadherin as well as the activity of actin regulators localized to adherens junctions are tightly controlled to facilitate cell junction assembly or disassembly in response to changes in external or internal forces and/or signaling. Phosphorylation of tyrosine, serine, or threonine residues acts as a switch on the majority of adherens junction proteins, turning ¡°on¡± or ¡°off¡± their interactions with other proteins and/or their enzymatic activity. Here, we provide an overview of the kinases and phosphatases regulating phosphorylation of adherens junction proteins and bring examples of phosphorylation events leading to the assembly or disassembly of adherens junctions, highlighting the important role of phosphorylation switches in regulating their dynamics. 1. Introduction Adherens junctions (AJs) are cell-cell adhesion sites where calcium-dependent cadherin receptors bind with their extracellular domains to cadherins on opposing cells and with their cytoplasmic tails connect¡ªvia adaptors¡ªto filamentous actin [1, 2]. By essentially providing a physical link between the actin cytoskeleton of neighboring cells AJs facilitate the integration of individual cells into a tissue. Additionally, AJs are instrumental in setting up and maintaining the apicobasal polarity of epithelial cells [3, 4], they function as mechanosensors [5] and serve as a nexus for signaling affecting important cell decisions, such as survival and differentiation [6]. During the development and lifetime of an organism, cells frequently change shape and position relative to their neighbors. Hence, the ability of cells to regulate their adhesive interactions plays a key role during tissue morphogenesis, repair, and renewal [3, 7, 8]. Defects in the adhesive characteristics of epithelial cells are pathological signs and loss of cell-cell adhesion can generate dedifferentiation and invasiveness of human carcinoma cells [9]. Thus, there is great interest in understanding the factors that affect assembly and disassembly of cell-cell adhesion at the molecular level. When considering regulatory mechanisms controlling AJ proteins, we distinguish between three subsequent steps of regulation: synthesis, localization, and activation. First, a cell controls whether proteins are synthesized or not. Indeed, transcriptional regulation of E-cadherin, notably by the snail transcription factor, plays an important role in
%U http://www.hindawi.com/journals/jst/2012/125295/