Aufsatz in einer Fachzeitschrift
cAMP-Dependent Protein Kinase and cGMP-Dependent Protein Kinase as Cyclic Nucleotide Effectors
Details zur Publikation
Autor(inn)en: | Lorenz, R.; Bertinetti, D.; Herberg, F. |
Publikationsjahr: | 2017 |
Zeitschrift: | Handbook of Experimental Pharmacology |
Seitenbereich: | 105-122 |
Jahrgang/Band : | 238 |
ISSN: | 0171-2004 |
eISSN: | 1865-0325 |
DOI-Link der Erstveröffentlichung: |
URN / URL: |
Zusammenfassung, 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.
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.
Schlagwörter
Animals, Binding Sites, Catalytic Domain, Cyclic AMP-Dependent Protein Kinases/chemistry/metabolism, Cyclic AMP/metabolism, Cyclic GMP-Dependent Protein Kinases/chemistry/metabolism, Cyclic GMP/metabolism, E0399OZS9N (Cyclic AMP), EC 2.7.11.11 (Cyclic AMP-Dependent Protein Kinases), EC 2.7.11.12 (Cyclic GMP-Dependent Protein Kinases), H2D2X058MU (Cyclic GMP), Humans, Protein Conformation, Second Messenger Systems, Structure-Activity Relationship, Substrate Specificity
