EP2 and EP4 prostanoid receptor signaling

Life Sci. 2003 Dec 5;74(2-3):143-53. doi: 10.1016/j.lfs.2003.09.031.


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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.
  • Review

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Humans
  • Mice
  • Mice, Knockout
  • Molecular Sequence Data
  • Receptors, Prostaglandin E / physiology*
  • Receptors, Prostaglandin E, EP2 Subtype
  • Receptors, Prostaglandin E, EP4 Subtype
  • Second Messenger Systems / genetics
  • Second Messenger Systems / physiology
  • Signal Transduction / genetics
  • Signal Transduction / physiology*


  • PTGER2 protein, human
  • PTGER4 protein, human
  • Ptger2 protein, mouse
  • Ptger4 protein, mouse
  • Receptors, Prostaglandin E
  • Receptors, Prostaglandin E, EP2 Subtype
  • Receptors, Prostaglandin E, EP4 Subtype