Departamento de Biología Molecular and Centro de Biología Molecular Severo Ochoa, Consejo Superior de Investigaciones Cientificas, Universidad Autónoma de Madrid, Madrid, Spain.
Cell Adh Migr. 2012 Nov-Dec;6(6):495-501. doi: 10.4161/cam.21585. Epub 2012 Oct 17.
G protein-coupled receptor kinase 2 (GRK2) is emerging as a key integrative node in cell migration control. In addition to its canonical role in the desensitization of G protein-coupled receptors involved in chemotaxis, novel recently identified GRK2 substrates and interacting partners appear to mediate the GRK2-dependent modulation of diverse molecular processes involved in motility, such as gradient sensing, cell polarity or cytoskeletal reorganization. We have recently identified an interaction between GRK2 and histone deacetylase 6 (HDAC6), a major cytoplasmic α-tubulin deacetylase involved in cell motility and adhesion. GRK2 dynamically associates with and phosphorylates HDAC6 to stimulate its α-tubulin deacetylase activity at specific cellular localizations such as the leading edge of migrating cells, thus promoting local tubulin deacetylation and enhanced motility. This GRK2-HDAC6 functional interaction may have important implications in pathological contexts related to aberrant epithelial cell migration.
G 蛋白偶联受体激酶 2（GRK2）作为细胞迁移调控中的关键整合节点正在出现。除了其在趋化作用涉及的 G 蛋白偶联受体脱敏中的典型作用外，最近新鉴定的 GRK2 底物和相互作用伙伴似乎介导了与运动相关的不同分子过程的 GRK2 依赖性调节，例如梯度感应、细胞极性或细胞骨架重排。我们最近发现了 GRK2 和组蛋白去乙酰化酶 6（HDAC6）之间的相互作用，HDAC6 是一种主要的细胞质α-微管蛋白去乙酰化酶，参与细胞运动和黏附。GRK2 动态地与 HDAC6 结合并磷酸化它，以刺激其在特定细胞定位（例如迁移细胞的前缘）的α-微管蛋白去乙酰化酶活性，从而促进局部微管蛋白去乙酰化和增强运动性。这种 GRK2-HDAC6 功能相互作用可能在与异常上皮细胞迁移相关的病理情况下具有重要意义。
