G protein-coupled receptor kinase 6 (GRK6)

G protein-coupled receptor kinase 6 (GRK6) is a serine/threonine protein kinase belonging to the G protein-coupled receptor kinase family, specifically the GRK4 subfamily. The GRK6 protein phosphorylates activated GPCRs, promoting arrestin binding, leading to receptor desensitization, internalization, and arrestin-mediated signaling. GRK6 is broadly expressed, with high levels in immune cells, where it regulates chemotaxis and inflammatory responses. Altered GRK6 activity is associated with pathological pain, neurodegenerative disease, and inflammatory disorders. The protein exists in multiple splice variants that affect its membrane association and function. GRK6 is being investigated as a therapeutic target, though as of 2024, no drugs are approved that selectively modulate its activity[1][5][7][8].

Other names

GRK6GPRK6G protein-coupled receptor kinase 6A/B/C (splice variants)

Inhibition of GRK6 leads to increased signaling via specific GPCRs (potentially relevant for Parkinson's, inflammatory disorders)[1][5][6]. Upregulation or activation of GRK6 may enhance receptor desensitization and arrestin-mediated signaling, possibly modulating inflammation and pain pathways[1][7].