FIG. 6.

The proposed model for the signaling pathways involved in 8-Bromo cAMP-induced mESC migration through adherent junction disruption and actin cytoskeleton rearrangement. Elevated intracellular cAMP by 8-Bromo cAMP stimulated both PKA and Epac, which subsequently activated Rac1 and Cdc42. 8-Bromo cAMP-induced activation of Rac1/Cdc42 increased MLCK expression and MLC phosphorylation, which resulted in disruption of cellular junctions (adherens junction, tight junction, and gap junction). In addition, 8-Bromo cAMP-induced activation of Rac1/Cdc42 also elicited activation of PKA, Arp, TOCA, and N-WASP and stimulated dephosphorylation of cofilin, which evoked the F-actin rearrangement. This 8-Bromo cAMP-induced disruption of cell junctions and cytoskeleton remodeling stimulated mESC migration. Color images available online at www.liebertpub.com/scd