EP2 and EP4 prostanoid receptor signaling

The EP(2) and EP(4) prostanoid receptors are two of the four subtypes of receptors for prostaglandin E(2) (PGE(2)). 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 EP(2) receptor does this primarily through cAMP-dependent protein kinase (PKA), whereas the EP(4) utilizes phosphatidylinositol 3-kinase (PI3K) as well as PKA. In addition, we have shown that the EP(4) receptor, but not the EP(2), 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 PGE(2) in cancer and inflammatory disorders.