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Differential signaling pathway activation and gene regulation among three human prostaglandin E3 (EP3) receptors
Author(s) -
Israel Davelene Davinah,
Regan John W
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.5.a429
Subject(s) - signal transduction , gene isoform , biology , receptor , prostaglandin e2 receptor , protein kinase b , microbiology and biotechnology , microarray analysis techniques , alternative splicing , phosphorylation , gene expression , gene , biochemistry , agonist
The EP 3 receptor is one of four receptor subtypes for prostaglandin‐E 2 (PGE 2 ). In humans, alternative mRNA splicing gives rise to eight isoforms of this receptor. The present study examined the second messenger signaling of the EP 3I , 3II , and 3III isoforms and their gene expression profiles. HEK cells stably expressing the EP 3I , 3II , and 3III receptor isoforms were examined with respect to activation of the mitogen activated protein kinase and the nuclear factor kappa B (NFκB) pathways. Treatment with PGE 2 resulted in the phosphorylation of ERKs 1 and 2 in EP 3II and EP 3III expressing cells but not in EP 3I expressing cells. This phosphorylation, however, only increased downstream ELK‐1 activity in EP 3III expressing cells. A second pathway examined was NFκB. Treatment with PGE 2 increased NFκB activity in EP 3II expressing cells via Gi, PI3K and AKT. The differential signaling of the EP3 receptor isoforms was further examined by microarray analysis, which indicated that ~10% of the genes were differentially expressed among the three isoforms. Quantitative PCR and western blot analysis were used to validate changes in the expression of genes identified in the microarray studies. In conclusion, our data suggest that the EP 3 receptor isoforms differ from one another with respect to both the activation of signal transduction pathways and the induction of gene expression. Supported by EY11291.