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Activated PAK then phosphorylates a serene residue (S665) within a conserved motif in the cytoplasmic tail of VE-cadherin. VE-cadherin is also phosphorylated by c-Src in a manner dependent on TSAD (Sun et al. 2012, Lambeng et al. 2005). Serine-phosphorylated VE-cadherin recruits beta-arrestin 2 which promotes the internalization of VE-cadherin into clathrin-coated pits. This process leads to the disassembly of endothelial-cell junctions, resulting in the enhanced permeability of the blood-vessel wall (Gavard & Gutkind 2006).