A model that envisions the p120/VE-cad complex as a key regulator of leukocyte TEM. (A) PMN interaction with adhesion molecules such as ICAM-1 on the endothelium surface triggers activation of src and other kinases. (B) Activation of kinases results in phosphorylation of VE-cad, dissociation of p120 from VE-cad, and opening of a junctional gap through which the PMN transmigrates. (C) Upon completion of TEM, p120 binds again to VE-cad as the gap reseals. (D) When p120 is overexpressed, receptor and nonreceptor tyrosine kinases fail to compete with the high levels of p120 present in the cytosol, VE-cad cannot be phosphorylated, and p120 is not released from the VE-cad complex. (E,F) This results in a lack of displacement of VE-cad and lack of gap formation, leading to diminished of PMN TEM.