EP₂ and EP₄ prostanoid receptor signaling

The EP₂ and EP₄ prostanoid receptors are two of the four subtypes of receptors for prostaglandin E₂ (PGE₂). They are in the family of G-protein coupled receptors and both receptors were initially characterized as coupling to Gs and increasing intracellular cAMP formation. Recently, however, we have shown that both receptors can stimulate T-cell factor (Tcf) mediated transcriptional activity. The EP₂ receptor does this primarily through cAMP-dependent protein kinase (PKA), whereas the EP₄ utilizes phosphatidylinositol 3-kinase (PI3K) as well as PKA. In addition, we have shown that the EP₄ receptor, but not the EP₂, can activate the extracellular signal-regulated kinases (ERKs) 1 and 2 by way of PI3K leading to the induction of early growth response factor-1 (EGR-1), a transcription factor traditionally associated with wound healing. This induction of EGR-1 expression has significant implications concerning the potential role of PGE₂ in cancer and inflammatory disorders.