Fig. 1.

Intracellular Ca²⁺ signaling in endothelial cells associated with vascular leakage and inflammation. Increase in cytosolic Ca²⁺ concentration activates specific kinases and phosphatases that, in turn, promote vascular leakage and inflammation. The serine/threonine kinase PKCα induces phosphorylation of p120-catenin and, through this mechanism, contributes to disassembly of AJs. PKCα also promotes reorganization of actin cytoskeleton and acto-myosin contractility by activating RhoA signaling. CaM-dependent activation of both MLCK-210 and CaMKII facilitates reorganization of actin cytoskeleton through the phosphorylation of actin motor myosin-II and caldesmon. In addition, CaM activates the phosphatase CaN, which dephosphorylates the microtubule accessory factor EB3, thereby coordinating reorganization of the actin and microtubule cytoskeleton. CaN also mediates activation of NFAT and promotes cytokine production by endothelium