Prostaglandin E2 induced functional expression of early growth response factor-1 by EP4, but not EP2, prostanoid receptors via the phosphatidylinositol 3-kinase and extracellular signal-regulated kinases

Hiromichi Fujino, Wei Xu, John W. Regan

Research output: Contribution to journalArticle

238 Scopus citations

Abstract

Prostaglandin E2 (PGE2) mediates its physiological effects by interactions with a subfamily of G-protein-coupled receptors known as EP receptors. These receptors consist of four primary subtypes named EP1, EP2, EP3, and EP4. The EP2 and EP4 subtypes are known to couple to Gαs and stimulate intracellular cyclic 3,5-adenosine monophosphate formation, whereas the EP1 and EP3 receptors are known to couple to Gαq and Gαi, respectively. Recently we found that EP2 and EP4 receptors can activate T-cell factor signaling; however, EP2 receptors did this primarily through a cAMP-dependent protein kinase-dependent pathway, whereas EP4 receptors primarily utilized a phosphatidylinositol 3-kinase (PI3K)-dependent pathway (Fujino, H., West, K. A., and Regan, J. W. (2002) J. Biol. Chem. 277, 2614-2619). We now report that PGE2 stimulation of EP4 receptors, but not EP2 receptors, leads to phosphorylation of the extracellular signal-regulated kinases (ERKs) through a PI3K-dependent mechanism. Furthermore, this activation of PI3K/ERK signaling by the EP4 receptors induces the functional expression of early growth response factor-1 (EGR-1). Under the same conditions induction of EGR-1 protein expression was not observed following PGE2 stimulation of EP2 receptors. These findings point to important differences in the signaling potential of the EP2 and EP4 receptors, which could be significant with respect to the potential involvement of EP4 receptors in inflammation and cancer.

Original languageEnglish (US)
Pages (from-to)12151-12156
Number of pages6
JournalJournal of Biological Chemistry
Volume278
Issue number14
DOIs
StatePublished - Apr 4 2003

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Fingerprint Dive into the research topics of 'Prostaglandin E<sub>2</sub> induced functional expression of early growth response factor-1 by EP<sub>4</sub>, but not EP<sub>2</sub>, prostanoid receptors via the phosphatidylinositol 3-kinase and extracellular signal-regulated kinases'. Together they form a unique fingerprint.

  • Cite this