Prostaglandin E receptor 4 (EP4) (EP4)

Prostaglandin E receptor 4 (EP4) is a G protein-coupled receptor (GPCR) that serves as a high-affinity receptor for prostaglandin E2 (PGE2), a key lipid mediator in inflammation and physiological homeostasis (UniProt P35408). Encoded by the PTGER4 gene, EP4 primarily signals through the Gs protein to stimulate adenylyl cyclase, resulting in elevated intracellular cyclic AMP (cAMP) levels and the activation of downstream pathways like PKA and PI3K (NCBI Gene 5734). It is widely expressed across various tissues, where it regulates diverse functions including vascular tone, renal water reabsorption, and bone remodeling. In the context of oncology, EP4 is frequently overexpressed and plays a pivotal role in promoting tumor growth, angiogenesis, and immune evasion by suppressing the activity of T cells and natural killer cells while enhancing the function of myeloid-derived suppressor cells (PMID: 30104715). Consequently, EP4 has emerged as a significant therapeutic target, with antagonists being developed to enhance the efficacy of cancer immunotherapies and agonists being explored for treating inflammatory bowel disease and osteoporosis (PubMed: 29653988).

Other names

PTGER4Prostanoid EP4 receptorPGE receptor EP4 subtypeProstaglandin E2 receptor EP4 subtype

EP4 antagonists inhibit the binding of PGE2 to the EP4 receptor, thereby blocking the Gs-protein-mediated increase in cAMP that leads to immunosuppression in the tumor microenvironment and inflammatory signaling (PMID: 30104715). EP4 agonists mimic PGE2 binding to activate the Gs-adenylyl cyclase pathway, promoting vasodilation, cytoprotection, and bone formation (UniProt P35408).