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Weibel–Palade bodies (WPBs) function as storage vesicles for von Willebrand factor (VWF) and a number of other bioactive compounds, including angiopoietin‐2 and insulin‐like growth factor‐binding protein 7. WPBs release their content following stimulation with agonists that increase the level of intracellular Ca²⁺, such as thrombin, or agonists that increase intracellular levels of cAMP, such as epinephrine.

Previously, we have shown that the exchange protein activated by cAMP, exchange protein activated by cAMP, and the small GTPase Rap1 are involved in cAMP‐mediated release of WPBs. In this study, we explored potential downstream effectors of Rap1 in cAMP‐mediated WPB release.

Studies were performed in primary human umbilical vein endothelial cells. Activation of the small GTP‐binding protein Rac1 was monitored by its ability to bind to the CRIB domain of the serine …