Why PGD2 has different functions from PGE2. (9th November 2020)

• Record Type: Journal Article
• Authors: Fujino, Hiromichi
• Is Part Of: BioEssays. Volume 43:Number 2(2021)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2020-11-09
• Subjects: biased ligand -- DP receptors -- EP2 receptors -- prostaglandin D2 -- prostaglandin E2; Molecular biology -- Periodicals; Cytology -- Periodicals; Developmental biology -- Periodicals; 572.8
• DOI: 10.1002/bies.202000213
• Languages: English
• ISSNs: 0265-9247

Abstract

Abstract: Prostaglandin (PG) D2 and PGE2 are positional isomers; however, they sometimes exhibit opposite physiological functions, such as in cancer development. Because DP receptors are considered to be a duplicated copy of EP2 receptors, PGD2 and PGE2 cross‐react with both receptors. These prostanoids may act as biased agonists for each receptor. In reviewing this field, a hypothesis was proposed to explain the opposed effects of these prostanoids from the viewpoints of the evolution of, mutations in, and biased activities of their receptors. Previous findings showing more mutations/variations in DP receptors than EP2 receptors among individuals worldwide indicate that DP receptors are still in a rapid evolutionary stage. The opposing effects of these prostanoids on cancer development may be attributed to the biased activity of PGE2 for DP receptors, which may incidentally develop during the process of the old ligand, PGE2 gaining selectivity to newly diverged DP receptors. Abstract : PGE2 and PGD2 sometimes exhibit opposite functions, such as in cancer development, which may be attributed to the biased activity of PGE2 for DP receptor, and may be incidentally developed by neo‐functionalization; in which one copy of the duplicated pair acquires novel function(s).