♦ See referenced article, J. Biol. Chem. 2012, 287, 26168–26176
Nitric oxide is a critical signaling molecule whose production is tightly controlled in vascular endothelial cells. The molecule is produced by endothelial nitric-oxide synthase (eNOS), which converts l-arginine into l-citrulline and NO. l-Citrulline is recycled back into l-arginine by two enzymes, argininosuccinate lyase and argininosuccinate synthase (AS). The action of AS is the rate-limiting step in NO production. Despite its importance, little is known about how the enzyme is regulated. In this Paper of the Week, a team led by Duane C. Eichler at the University of South Florida demonstrated that when endothelial cells were stimulated with calcium, protein kinase Cα phosphorylated AS at Ser-328 and promoted its action. The phosphorylation of AS occurred at the same time as the phosphorylation of eNOS. The authors concluded, “these results represent the first demonstration of a biologically relevant phosphorylation site for AS and are consistent with previous findings demonstrating the coordinate regulation of eNOS and AS relative to vascular endothelial NO production.”
Phosphorylation of Ser-328 in argininosuccinate synthase.