Prostaglandin E2 receptor 2 (EP2) (EP2)

The Prostaglandin E2 receptor 2 (EP2), also known as PTGER2, is a G protein-coupled receptor that binds prostaglandin E2 (PGE2), a key lipid mediator derived from arachidonic acid via cyclooxygenase-2 (COX-2). EP2 primarily signals through Gs proteins to stimulate adenylate cyclase, elevating intracellular cAMP levels and activating effectors like protein kinase A (PKA) and exchange protein activated by cAMP (Epac), which regulate processes such as cell proliferation, migration, and immune modulation.[1][2][4][6] It also engages β-arrestin-mediated G protein-independent pathways, activating PI3K/Akt, ERK, JNK, and EGFR to promote tumor growth, invasion, angiogenesis, and immune suppression in contexts like cancer and chronic inflammation.[2][4][6] In immune cells such as dendritic cells and T cells, EP2 modulates maturation, Th17 differentiation, and cytokine production, contributing to both pro- and anti-inflammatory responses.[1][9] Dysregulated EP2 signaling drives pathologies including colorectal cancer, neurodegenerative diseases (e.g., Alzheimer's, Parkinson's via neuroinflammation), endometriosis, and epilepsy, positioning it as an emerging therapeutic target for selective antagonists like TG4-155, though agonists show promise in muscle regeneration and stroke models.[2][3][14] Challenges include its context-dependent roles and lack of approved drugs, with potential cardiovascular risks from pathway modulation.[2][5]

Other names

PTGER2Prostaglandin E receptor 2 subtypePGE2 receptor EP2 subtype

Gs-coupled: Activates adenylate cyclase to elevate cAMP, activating PKA or Epac for downstream effects (e.g., CREB phosphorylation, neuronal survival) G protein-independent (β-arrestin): Activates PI3K/Akt, ERK, JNK, Src, EGFR pathways promoting proliferation, migration, tumor growth Antagonism blocks pro-inflammatory, pro-tumor effects in disease models