cGMP Signaling through cAMP- and cGMP-Dependent Protein Kinases

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Publisher Summary

The signaling pathways by which nitric oxide (NO) affects cell function, are by no means limited to the stimulation of guanylate cyclase. Concentrations of NO that activate guanylate cyclase may also have other effects on cells. This is because, at least in part, of the fact that NO binds with high affinity to heme moieties in proteins—guanylate cyclase being the only example of a heme-containing enzyme. At high concentrations of NO, that is, those that might be realized as a consequence of the induction on NO synthase by cytokines and other biological modifier molecules, enzymes containing iron-sulfur groups bind NO. One of the recently described mechanisms of NO signaling, at least in terms of its pathophysiological effects on cells, is the formation of peroxynitrite. NO reacts with superoxide generated in response to cellular responses to oxidative injury to form the free radical peroxynitrite. Peroxynitrite, in turn, may have a variety of effects on cells, including orthonitration of tyrosine residues on proteins. The significance of this effect of NO is not clear at this time, but peroxynitrite production and protein “nitration” have been correlated with tissue injury and pathological responses of the tissues to insult.

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