PGE2-EP receptor signaling pathways

PGE2-EP receptor signaling pathways. Four major types of EP receptors are involved in the signaling pathway mediated via different G proteins (p/q, αs and αi) using different second messenger. PGE2 induces intracellular Ca2+ or cAMP when it couples and signals through EP1 or EP2/4 receptors respectively. However, it reduces intracellular cAMP when it signals through EP3 receptors. Several different kinases are involved in PGE2 induced signaling pathways. PGE2-EP4 receptor coupling induces TNFα, cyclin D and angiogenesis using a specific pathway that is mediated via different MAP kinases. PGE2 also promotes cancer cell proliferation and inhibits apoptosis. It also induces COX-2 gene transcription and induces cell proliferation. On the other hand, it could also inhibit cell cycle through phosphorylation of Akt, GSK-3β and β-catenin. Abbreviations: AC, adenylate cyclase; DAG, diacylglycerol; IP3, inositol triphosphate; PIP2, phosphatidylinositol diphosphate; PKA, protein kinase A; PKC, protein kinase C; PI3K, phosphoinositide-3-kinase; Akt, protein kinase B; ERK, extracellular signal-regulated protein kinase; JNK, c-Jun N-terminal kinase; EGR-1, early growth response 1; EGFR, epidermal growth factor receptor; FGFR, fibroblast growth factor receptor; GSK-3, glycogen synthase kinase-3; ®, phosphorylation; ↑, up regulated; ↓, down regulated; X, inhibition.

Publication

Prostaglandin E2 receptor distribution and function in the gastrointestinal tract. (2006) I Dey, et al. Br J Pharmacol. 2006 Nov;149(6):611-623. Figure: F2. All organisms Homo sapiens Mus musculus Drosophila melanogaster

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