Calmodulin dependent protein kinase II CaMKII

In addition to the calcium-dependent activation, the activity of eNOS can also be regulated positively or negatively by the phosphorylation of the enzyme. Indeed, it has been reported that phosphorylation of the residues serine 1177 or 615 activates eNOS while the phosphorylation of the residue threonine 495, tyrosine 657, or serine 114 causes an inhibitory posttranslational modification [34]. Activation of eNOS subsequent to its phosphorylation on serine 1177 in endothelial cells has been observed in response to shear stress, bradykinin, and VEGF [34]. Several kinases are involved in the phosphorylation of serine 1177 including the protein kinase A (PKA), protein kinase B (Akt), or Ca /calmodulin-dependent protein kinases II (CaMKII) (for review, see [34]). On the other hand, eNOS is constitutively phosphorylated on threonine 495. This phosphorylation is associated in endothelial cells with a reduced binding ability of the calcium-calmoduUn complex to eNOS [35]. 

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