G protein-coupled receptor kinase 4 (GRK4)

G protein-coupled receptor kinase 4 is an enzyme encoded by the GRK4 gene, part of the GRK subfamily of serine/threonine kinases[1][12]. GRK4 specifically phosphorylates activated GPCRs, promoting arrestin binding and subsequent receptor desensitization, internalization, and signaling modulation[1][2][12]. It is highly expressed in the testes, with lower expression in the brain, kidney, and other tissues[1]. GRK4 plays a pivotal role in modulating dopamine and angiotensin II receptor functions in the kidney, affecting sodium balance and blood pressure regulation[2][5]. Variations in GRK4 are genetically linked to both essential and secondary hypertension, making it a target for novel antihypertensive therapies[2][4][5]. Therapeutic inhibitors of GRK4 are being investigated for cardiovascular disease modulation[11][13]. GRK4 interacts directly with several GPCRs, influencing response to drugs and serving as a biomarker for hypertension risk[2][5]. Notable safety concerns include potential blood pressure disturbances if GRK4 activity is dysregulated[2][10].

Other names

GRK4GPRK2LGPRK4G protein-coupled receptor kinase GRK4IT11ITI1GRK4aG protein-coupled receptor kinase 2-like

Inhibition of kinase activity (blockade of GRK4's GPCR regulation); Modulation of receptor phosphorylation and desensitization