HIV-1 Tat C mediated tyrosine phosphorylation of VE-cadherin complex and increase in permeability of hBMVECs. HIV-1 Tat C treatment induces the intracellular ROS generation by activating NADPH oxidases (NOX2/NOX4) proteins in hBMVECs. Elevated intracellular levels of ROS activate the levels of redox sensitive kinase PYK2, which led to increased tyrosine phosphorylation of β-catenin and VE-cadherin. HIV-1 Tat C treatment also downregulates major phosphatases VE-PTP and SHP2 and leads to their dissociation from VE-cadherin complex. These shift in PTK/ PTP ratio in hBMVECs after HIV-1 Tat C exposure leads to destabilized junctional assembly and thereby enhanced endothelial permeability.