Abstract
The cAMP-dependent protein kinase (PKA) and the cGMP-dependent protein kinase (PKG) are homologous enzymes with different binding and activation specificities for cyclic nucleotides. Both enzymes harbor conserved cyclic nucleotide-binding (CNB) domains. Differences in amino acid composition of these CNB domains mediate cyclic nucleotide selectivity in PKA and PKG, respectively. Recently, the presence of the noncanonical cyclic nucleotides cCMP and cUMP in eukaryotic cells has been proven, while the existence of cellular cIMP and cXMP remains unclear. It was shown that the main effectors of cyclic nucleotide signaling, PKA and PKG, can be activated by each of these noncanonical cyclic nucleotides. With unique effector proteins still missing, such cross-activation effects might have physiological relevance. Therefore, we approach PKA and PKG as cyclic nucleotide effectors in this chapter. The focus of this chapter is the general cyclic nucleotide-binding properties of both kinases as well as the selectivity for cAMP or cGMP, respectively. Furthermore, we discuss the binding affinities and activation potencies of noncanonical cyclic nucleotides.
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Lorenz, R., Bertinetti, D., Herberg, F.W. (2015). cAMP-Dependent Protein Kinase and cGMP-Dependent Protein Kinase as Cyclic Nucleotide Effectors. In: Seifert, R. (eds) Non-canonical Cyclic Nucleotides. Handbook of Experimental Pharmacology, vol 238. Springer, Cham. https://doi.org/10.1007/164_2015_36
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