MAP kinases bind endothelial nitric oxide synthase

Endothelial nitric oxide synthase (eNOS) contains a motif similar to recognition sequences in known MAPK binding partners. In optical biosensing experiments, eNOS bound p38 and ERK with similar to 100 nM affinity and complex kinetics. Binding is diffusion-limited (k(on) similar to.15 x 10(6) M-1 s(-1)). Neuronal NOS also bound p38 but exhibited much slower and weaker binding. p38-eNOS binding was inhibited by calmodulin. Evidence for a ternary complex was found when eNOS bound p38 was exposed to CaM, increasing the apparent dissociation rate. These observations strongly suggest a direct role for MAPK in regulation of NOS with implications for signaling pathways including angiogenesis and control of vascular tone. (C) 2012 Federation of European Biochemical Societies. Published by Elsevier B. V. All rights reserved.