Departamento de Biología Molecular and Centro de Biología Molecular "Severo Ochoa" (Consejo Superior de Investigaciones Científicas - Universidad Autónoma de Madrid), Universidad Autónoma de Madrid, 28049 Madrid, Spain; Instituto de Investigación Sanitaria La Princesa, 28006 Madrid, Spain.
Departamento de Biología Molecular and Centro de Biología Molecular "Severo Ochoa" (Consejo Superior de Investigaciones Científicas - Universidad Autónoma de Madrid), Universidad Autónoma de Madrid, 28049 Madrid, Spain; Instituto de Investigación Sanitaria La Princesa, 28006 Madrid, Spain.
Curr Opin Cell Biol. 2014 Apr;27:10-7. doi: 10.1016/j.ceb.2013.10.005. Epub 2013 Nov 16.
G protein-coupled receptor kinases (GRKs) are emerging as important integrative nodes in cell migration processes. Recent evidence links GRKs (particularly the GRK2 isoform) to the complex modulation of diverse aspects of cell motility. In addition to its well-established role in the desensitization of G protein-coupled receptors involved in chemotaxis, GRK2 can play an effector role in the organization of actin and microtubule networks and in adhesion dynamics, by means of novel substrates and transient interacting partners, such as the GIT1 scaffold or the cytoplasmic α-tubulin deacetylase histone deacetylase 6 (HDAC6). The overall effect of altering GRK levels or activity on chemotaxis would depend on how such different roles are integrated in a given cell type and physiological context, and may have relevant implications in inflammatory diseases or cancer progression.
G 蛋白偶联受体激酶(GRKs)正在成为细胞迁移过程中重要的综合节点。最近的证据将 GRKs(特别是 GRK2 同工型)与细胞运动的不同方面的复杂调节联系起来。除了其在参与趋化作用的 G 蛋白偶联受体脱敏中的既定作用外,GRK2 还可以通过新型底物和瞬时相互作用的伴侣(如 GIT1 支架或细胞质α-微管蛋白去乙酰化酶组蛋白去乙酰化酶 6(HDAC6)),在肌动蛋白和微管网络的组织和黏附动力学中发挥效应子作用。改变 GRK 水平或活性对趋化作用的总体影响将取决于在特定细胞类型和生理环境中如何整合这些不同的作用,并且可能在炎症性疾病或癌症进展中具有相关意义。