FIG. 7.

A model for VEGF-induced, SERCA2b C674-dependent Ca²⁺ influx in ECs. VEGF stimulation promotes the production of ^•NO by eNOS, leading to S-glutathiolation of the SERCA2b-reactive cysteine-674 and activation of SERCA2b. Ca²⁺ is pumped by SERCA2b into the ER, where it is then released by the RyR, eliciting continued activation of eNOS. Additionally, activation of the plasma membrane Ca²⁺ channel, Orai1, stimulates Ca²⁺ influx from the extracellular space into the cytosol, further stimulating eNOS and stimulating EC migration. eNOS, endothelial nitric oxide synthase; RyR, ryanodine receptor.