Figure 8. Divergent pathways promoted by PGE ₂ synergistically activate the transcription factor MEF2.

Schematic representation of the PGE₂ triggered signal transduction pathways converging on HDAC5 and subsequently MEF2. PGE₂ activates MEF2 through EP₃ receptor and the βγ subunit of G_i/o proteins. One pathway implicates activation of PKD and concomitant phosphorylation of HDAC5. The phosphorylated HDAC5 is exported from the nucleus, which results in de‐repression of MEF2 and activation of the embryonic gene programs. In addition, hand in hand activation of Tiam1, Rac1, and PAK2 kinase occurs, which pathway also contributes to the nuclear export of HDAC5 and is responsible for synergistic activation of MEF2.