cGMP-dependent protein kinase protects cGMP from hydrolysis by phosphodiesterase-5
| Autor: | Jackie D. Corbin, Sharron H. Francis, Jun Kotera, Kennard A. Grimes |
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| Rok vydání: | 2003 |
| Předmět: |
DNA
Complementary Allosteric regulation Phosphodiesterase 3 Biology Biochemistry Enzyme activator Allosteric Regulation 3' 5'-Cyclic-GMP Phosphodiesterases Cyclic GMP-Dependent Protein Kinases Animals Phosphorylation Protein kinase A Cyclic GMP Molecular Biology Cyclic GMP-Dependent Protein Kinase Type I Cyclic Nucleotide Phosphodiesterases Type 5 Binding Sites Phosphoric Diester Hydrolases Hydrolysis Autophosphorylation Cell Biology Recombinant Proteins Enzyme Activation cGMP-specific phosphodiesterase type 5 Mutation Mutagenesis Site-Directed cardiovascular system Cattle PDE10A Dimerization cGMP-dependent protein kinase Protein Binding Research Article |
| Zdroj: | Biochemical Journal. 372:419-426 |
| ISSN: | 1470-8728 0264-6021 |
| DOI: | 10.1042/bj20030107 |
| Popis: | The physiological effects of cGMP are largely determined by the activities of intracellular receptors, including cGMP-dependent protein kinase (PKG) and cGMP-binding cyclic nucleotide phosphodiesterases (PDEs), and the distribution of cGMP among these receptors dictates activity of the signalling pathway. In the present study, the effects of PKG-Ialpha or PKG-Ibeta on the rate of cGMP hydrolysis by the isolated PDE5 catalytic domain were examined. PKG-Ialpha strongly inhibited cGMP hydrolysis with an IC(50) value of 217 nM, which is similar to the physiological concentration of PKG in pig coronary artery reported previously. By contrast, PKG-Ibeta, which has lower affinity for cGMP than does PKG-Ialpha, inhibited cGMP hydrolysis with an IC(50) of approx. 1 microM. Inhibition by PKG-Ialpha was more effective than that by PKG-Ibeta, consistent with their relative affinities for cGMP. Autophosphorylation of PKGs increased their cGMP-binding affinities and their inhibitory effects on PDE5 hydrolysis of cGMP. Autophosphorylation of PKG-Ibeta increased its inhibitory potency on PDE5 hydrolysis of cGMP by 10-fold compared with a 2-fold increase upon autophosphorylation of PKG-Ialpha. The results indicate that cGMP bound to allosteric cGMP-binding sites of PKG is protected from hydrolysis by PDE5 and that persistent protection of cGMP by either non-phosphorylated or autophosphorylated PKGs may be a positive-feedback control to sustain cGMP signalling. |
| Databáze: | OpenAIRE |
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