When lymphocyte α4β1 integrin (dark green dimer) binds to endothelial VCAM-1 (turquoise) or VEGF (yellow spheres) binds VEGF receptor 2 (top right, orange), a signaling cascade is set in motion that leads to activation of Rac1 (GTP bound). Rac1 in turn activates NOX, which converts molecular oxygen to ROS. These ROS activate the kinase Pyk2, which phosphorylates an unidentified substrate (yellow) for VE-PTP and causes VE-PTP (red) to dissociate from VE cadherin (purple). This dissociation is associated with increased leukocyte transmigration and increased macromolecular permeability. See Figure 7D in the paper by Vockel and Vestweber that begins on page 2512. Professional illustration by Debra T. Dartez