G-protein coupled receptor kinase 2 (GRK2), also referred as Adrenergic, beta, receptor kinase 1 (ADRBK1), is a ubiquitous member of the G protein-coupled receptor kinase (GRK) family that appears to play a central, integrative role in signal transduction cascades. GRK2 can phosphorylate a growing number of non-GPCR substrates and associate with a variety of proteins related to signal transduction, thus suggesting that this kinase could also have diverse 'effector' functions. GRK2 has been reported to interact with a variety of signal transduction proteins related to cell migration such as MEK, Akt, PI3Kgamma or GIT. Interestingly, the levels of expression and activity of this kinase are altered in a number of inflammatory disorders (as rheumatoid arthritis or multiple sclerosis), thus suggesting that GRK2 may play an important role in the onset or development of these pathologies. The important physiological function of GRK2 as a modulator of the efficacy of GPCR signal transduction systems is exemplified by its relevance in cardiovascular physiopathology as well as by its emerging role in the regulation of chemokine receptors. Besides its canonical role in the modulation of the signalling mediated by many G protein-coupled receptors (GPCR), this protein can display a very complex network of functional interactions with a variety of signal transduction partners, in a stimulus, cell type, or context-specific way.

β-Arrestin-1 (ARRB1) is a cytoplasmic protein that belongs to the arrestin family. ARRB1 is expressed at high levels in peripheral blood leukocytes and the central nervous system. ARRB1 regulates agonist-mediated G-protein coupled receptor (GPCR) signaling by mediating both receptor desensitization and resensitization processes. ARRB1 acts as a cofactor in the beta-adrenergic receptor kinase (BARK) mediated desensitization of beta-adrenergic receptors. ARRB1 is believed to play a major role in regulating receptor-mediated immune functions. ARRB1 is involved in Toll-like receptor and IL-1 receptor signaling through the interaction with TRAF6.