P2Y purinoceptor 8 (P2RY8)

P2Y purinoceptor 8 (P2RY8) is a G protein-coupled receptor that, in humans, is encoded by the P2RY8 gene[6][4][8]. It is a member of the purinergic receptor (P2Y receptor) family, which mediates cellular responses to extracellular nucleotides. Uniquely, P2RY8 is a high-affinity receptor for S-geranylgeranyl-glutathione (GGG), an endogenous metabolite present in lymphoid tissues[4][5][8]. Upon ligand binding, P2RY8 couples to the GNA13 intracellular signaling protein, suppressing AKT activation and thereby regulating the confinement and migration of B cells and T cells within germinal centers and bone marrow microenvironments[4][5][8]. Its physiologic expression is primarily found within immune tissues, where it plays an important role in lymphocyte homeostasis and immune cell positioning. Clinically, recurring mutations of P2RY8 are linked to certain lymphoid cancers, particularly diffuse large B-cell lymphoma[6]. No approved drugs currently target P2RY8, and its pharmacology remains incompletely characterized.

Other names

P2RY8P2Y8Purinergic receptor P2Y, G-protein coupled, 8S-geranylgeranyl-glutathione receptor P2RY8G-protein coupled purinergic receptor P2Y8P2Y receptor family member 8

Endogenous agonist: S-geranylgeranyl-glutathione (GGG) binds and activates P2RY8, coupling to GNA13 and leading to repression of AKT activation signaling in immune cells[4][5][8] No known synthetic drugs or antagonists currently characterized