Molecular basis for the potential role of GRK2 in pathological disorders.

G protein-coupled receptor kinase 2(GRK2) is a ubiquitous member of the family of GRKs that are serine/threonine kinases originally discovered for their role in the process of desensitization of agonist-activated G protein-coupled receptors (GPCRs). However, emerging evidence suggests that GRK2 can phosphorylate a large number of non-GPCR substrates and interact with a plethora of proteins involved in signaling and trafficking, suggesting that GRK2 would participate in the regulation of diverse cellular responses in a phosphorylation-dependent and -independent manner. Alternations in GRK2 levels and/or activity are demonstrated in an array of relevant cardiovascular, metabolic, inflammatory, or cancer pathologies. These changes are assumed to contribute to the onset and/or development of such pathologies. Thus, GRK2 may serve as a potentially interesting therapeutic target and those drugs targeted for GRK2 may constitute a novel therapeutic strategy for several intractable diseases, including sepsis.