EP2 and EP4 prostanoid receptor signaling

  • Regan J
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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.

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  • John W Regan

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