title: cAMP-Dependent Protein Kinase and cGMP-Dependent Protein Kinase as Cyclic Nucleotide Effectors.
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.
authors.affiliation: Department of Biochemistry, University of Kassel, Heinrich-Plett-Str. 40, 34132, Kassel, Germany.
authors.forename: Robin
authors.initials: R
authors.lastname: Lorenz
authors.affiliation: Department of Biochemistry, University of Kassel, Heinrich-Plett-Str. 40, 34132, Kassel, Germany.
authors.forename: Daniela
authors.initials: D
authors.lastname: Bertinetti
authors.affiliation: Department of Biochemistry, University of Kassel, Heinrich-Plett-Str. 40, 34132, Kassel, Germany. herberg@uni-kassel.de.
authors.forename: Friedrich W
authors.initials: FW
authors.lastname: Herberg
mesh_terms: D000818:Animals; D001665:Binding Sites; D020134:Catalytic Domain; D000242:Cyclic AMP / Q000378:metabolism*; D017868:Cyclic AMP-Dependent Protein Kinases / Q000737:chemistry / Q000378:metabolism*; D006152:Cyclic GMP / Q000378:metabolism*; D017869:Cyclic GMP-Dependent Protein Kinases / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D008958:Models, Molecular; D011487:Protein Conformation; D015290:Second Messenger Systems; D013329:Structure-Activity Relationship; D013379:Substrate Specificity
chemical_list: D000242:Cyclic AMP; D017868:Cyclic AMP-Dependent Protein Kinases; D017869:Cyclic GMP-Dependent Protein Kinases; D006152:Cyclic GMP
keywords: CNB domain; Cyclic nucleotides; PKA; PKG; Protein kinases; Selectivity; Specificity; cAMP; cCMP; cGMP; cIMP; cUMP; cXMP