Another activation switch for endothelial nitric oxide synthase: why does it have to be so complicated?

Regulation of the endothelial isoform of nitric oxide synthase (eNOS) appea rs to be much more complex in comparison to that of other NOS isoforms. A r ecent paper has expanded the regulation of the enzyme to the realm of sphin golipid signaling, specifically implicating that sphingosine I-phosphate, e ndothelial differentiation gene (Edg) receptors and Akt kinase induce a sig nal transduction pathway via phosphorylation of a serine residue in eNOS. B radykinin, a nonapeptide formed by enzymatic cleavage of a plasma protein p recursor, activates eNOS by an independent pathway that does not require se rine phosphorylation, suggesting a complex interplay of signals in the cont rol of endothelial formation of nitric oxide.