G protein-coupled receptor 132 (GPR132)

G protein-coupled receptor 132 (GPR132 or G2A) is a member of the proton-sensing G protein-coupled receptor subfamily, characterized by seven transmembrane domains. It functions predominantly as a sensor of extracellular pH and may serve as a receptor for oxidized polyunsaturated fatty acid metabolites, especially oxidized linoleic and arachidonic acid derivatives like 9-HODE, as well as N-palmitoylglycine. GPR132 is highly expressed in immune cells, including macrophages, lymphocytes, and natural killer cells, where it regulates functions such as cell migration, proliferation, differentiation, and responses to metabolic and inflammatory stimuli. It acts through G protein signaling (notably Gα_s and Gα_13) and is implicated in the regulation of cell cycle, apoptosis, immune responses, and maintenance of cellular homeostasis during oxidative stress. GPR132 has demonstrated roles in tumor suppression, modulation of NK cell cytotoxicity, and is involved in the pathogenesis of cholesterol gallstone disease. Its precise ligand profile and mechanisms continue to be actively studied[1][3][5][7][9].

Other names

G2AG2 accumulation protein

Activation via proton-sensing at acidic extracellular pH which leads to cellular signal transduction; Ligand binding (e.g., oxidized fatty acids, N-palmitoylglycine) triggers downstream G protein (mainly Gα_s and Gα_13) signaling and phospholipase C activation; Inhibition of immune cell cytotoxicity via Gα_s/CSK/ZAP70/NF-κB pathway in natural killer (NK) cells