EP2 and EP4 prostanoid receptor signaling

Abstract

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.