Figure 9.

Model for PAK induction of vascular permeability. PAK is activated in response to inflammatory, thrombotic, and angiogenic stimuli. Rac mediates activation of PAK, whereas Ras mediates activation of MEK and Erk. An atypical proline-rich sequence in PAK binds to the βPIX SH3 domain. PIX binds to GIT1 through a region in the C terminus of PIX and the SHD of GIT1. The SHD also binds MEK1/2. PAK phosphorylates MEK on ser298, which facilitates activation of MEK by Raf. Subsequent activation of Erk by MEK leads to activation of MLCK and contractility, which disrupts intercellular junctions.