Schematic representation of the proposed mechanism by which KLF2 inhibits JNK signaling and induces cell alignment through the actin cytoskeleton. Shear stress activates the MEK5/ERK5/MEF2 MAPK pathway that transcriptionally induces KLF2, which indirectly activates RhoA, which causes the formation of actin shear fibers. These fibers are both essential for the alignment in the direction of the flow and for inhibition of the FAK-JNK-c-Jun/ATF2 signaling pathway. Red arrows indicate activation; green blunted arrows indicate inhibition.