Differential activation of cAMP- and cGMP-dependent protein kinases by cyclic purine and pyrimidine nucleotides

Wolter, Sabine; Golombek, Marina; Seifert, Roland

doi:10.1016/j.bbrc.2011.10.093

Cited by 49 publications

(41 citation statements)

References 21 publications

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“…This proposal explicitly implies that cIMP must activate a different effector than PKG. The reduction of affinity of PKG for cIMP compared to cGMP by two orders of magnitude could be compatible with the assumption that cIMP bypasses this kinase (Wolter et al 2011) (Table 1), but what could then be the target of cIMP? Another straightforward candidate for cIMP could be cAMP-dependent protein kinase (PKA).…”

mentioning

confidence: 64%

“…1). The loss of the amino group results in a reduction in affinity of cIMP for the cGMP effector cGMPdependent protein kinase Iα (PKGIα) by more than two orders of magnitude (Wolter et al 2011) (Table 1).…”

mentioning

confidence: 99%

“…Another straightforward candidate for cIMP could be cAMP-dependent protein kinase (PKA). In fact, cIMP activates two isoforms of PKA (RIα and RIIα) with about tenfold higher potency than cGMP (Wolter et al 2011) (Table 1). However, an activation of PKA would also be expected to result in vasodilation, but not vasoconstriction (Pelligrino and Wang 1998).…”

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confidence: 99%

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Is cIMP a second messenger with functions opposite to those of cGMP?

Seifert

2014

Naunyn-Schmiedeberg's Arch Pharmacol

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Is cIMP a second messenger with functions opposite to those of cGMP?

Seifert

2014

Naunyn-Schmiedeberg's Arch Pharmacol

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“…Analysis of HEK-293 and B103 cells has demonstrated that cCMP is generated by soluble adenylyl cyclase in mammalian cells, reaching concentrations comparable to the established second messenger cGMP [4]. Since cCMP is biologically active [9,11,12], it is conceivable that its intracellular concentration has to be regulated, e.g. by the activity of PDEs.…”

Section: Discussionmentioning

confidence: 99%

“…The activity of hyperpolarization-activated cyclic nucleotidegated cation channel (HCN) ion channels is modulated by cCMP [9]. Furthermore, cCMP-agarose binds protein kinase A (PKA) [10] and cCMP regulates both PKA and protein kinase G (PKG) in vitro [11]. cCMP causes guanosine 3 0 ,5 0 -cyclic monophosphate (cGMP) kinase I activation and subsequent relaxation of murine aorta smooth muscle cells [12].…”

Section: Introductionmentioning

confidence: 99%

PDE7A1 hydrolyzes cCMP

et al. 2014

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a b s t r a c tThe degradation and biological role of the cyclic pyrimidine nucleotide cCMP is largely elusive. We investigated nucleoside 3 0 ,5 0 -cyclic monophosphate (cNMP) specificity of six different recombinant phosphodiesterases (PDEs) by using a highly-sensitive HPLC-MS/MS detection method. PDE7A1 was the only enzyme that hydrolyzed significant amounts of cCMP. Enzyme kinetic studies using purified GST-tagged truncated PDE7A1 revealed a cCMP K M value of 135 ± 19 lM. The V max for cCMP hydrolysis reached 745 ± 27 nmol/(min mg), which is about 6-fold higher than the corresponding velocity for adenosine 3 0 ,5 0 -cyclic monophosphate (cAMP) degradation. In summary, PDE7A is a high-speed and low-affinity PDE for cCMP.

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cAMP-Dependent Protein Kinase and cGMP-Dependent Protein Kinase as Cyclic Nucleotide Effectors

Lorenz

Bertinetti

2015

Non-Canonical Cyclic Nucleotides

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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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Differential activation of cAMP- and cGMP-dependent protein kinases by cyclic purine and pyrimidine nucleotides

Cited by 49 publications

References 21 publications

Is cIMP a second messenger with functions opposite to those of cGMP?

Is cIMP a second messenger with functions opposite to those of cGMP?

PDE7A1 hydrolyzes cCMP

cAMP-Dependent Protein Kinase and cGMP-Dependent Protein Kinase as Cyclic Nucleotide Effectors

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