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The G protein-coupled receptor kinase (GRK) interactome: Role of GRKs in GPCR regulation and signaling

2006; Elsevier BV; Volume: 1768; Issue: 4 Linguagem: Inglês

10.1016/j.bbamem.2006.09.019

1879-2642

Catalina Ribas, Petronila Penela, Cristina Murga, Alicia Salcedo, Carlota García‐Hoz, María Jurado-Pueyo, Ivette Aymerich, Federico Mayor,

Neuropeptides and Animal Physiology

G protein-coupled receptor kinases (GRKs) and arrestins are key participants in the canonical pathways leading to phosphorylation-dependent GPCR desensitization, endocytosis, intracellular trafficking and resensitization as well as in the modulation of important intracellular signaling cascades by GPCR. Novel studies have revealed a phosphorylation-independent desensitization mechanism operating through their RGS-homology (RH) domain and the recent determination of the crystal structures of GRK2 and GRK6 has uncovered interesting details on the structure-function relationships of these kinases. Emerging evidence indicates that the activity of GRKs is tightly modulated by mechanisms including phosphorylation by different kinases and interaction with several cellular proteins such as calmodulin, caveolin or RKIP. In addition, GRKs are involved in multiple interactions with non-receptor proteins (PI3K, Akt, GIT or MEK) that point to novel GRK cellular roles. In this article, our purpose is to describe the ever increasing map of functional interactions for GRK proteins as a basis to better understand its contribution to cellular processes.