The serine-threonine phosphatase calcineurin is a regulator of endothelial store-operated XXXX entry.

@entity2426 @entity7010 @entity593 @entity460 @entity5158
Disruption of the endothelium leads to increased permeability, allowing extravasation of macromolecules and other solutes from blood vessels. @entity460 entry through a @entity460 -selective, store-operated @entity460 (SOC) channel, I soc, contributes to barrier disruption. An understanding of the mechanisms surrounding the regulation of I soc is far from complete. We show that the @entity460 /calmodulin-activated phosphatase calcineurin (CN) plays a role in regulation of SOC entry, possibly through the dephosphorylation of @entity7010 ( @entity7010 ). Phosphorylation has been implicated as a regulatory mechanism of activity for a number of canonical transient receptor potential (TRPC) and SOC channels, including I soc. Our results show that @entity7010 phosphorylation increases in pulmonary artery endothelial cells (PAECs) upon activation of SOC entry. However, the phosphatases involved in @entity7010 dephosphorylation are unknown. We found that a CN inhibitor ( @entity5158 [ @entity5158 ]) increases the phosphorylation pattern of @entity7010 . Using a @entity593 -acetoxymethyl ester approach to measure cytosolic @entity460 in PAECs, we found that @entity5158 decreases SOC entry following @entity2426 treatment in PAECs. Luciferase assays indicate that @entity2426 induces activation of CN activity and confirm inhibition of CN activity by @entity5158 in PAECs. Also, I soc is significantly attenuated in whole-cell patch-clamp studies of PAECs treated with @entity5158 . Finally, PAECs pretreated with @entity5158 exhibit decreased interendothelial cell gap formation in response to @entity2426 -induced SOC entry, as compared to control cells. Taken together, our data show that CN contributes to the phosphorylation status of @entity7010 , which is important in regulation of endothelial SOC entry and I soc activity.
