Interaction of the catalytic subunit of protein kinase A with the lung type V cyclic GMP phosphodiesterase

modulation of non-catalytic binding sites

F Burns, N J Pyne

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20 Citations (Scopus)

Abstract

We have previously demonstrated that the catalytic sub-unit of protein kinase A can catalyse a potent activation of partially purified Type V cyclic GMP-specific phosphodiesterase activity (Burns et al., 1992, Biochem. J. 283, 487-491). We now demonstrate that this phosphodiesterase most likely has a sub-unit mass of 90kDa, based upon 32P-cyclic GMP photo-affinity labelling, that activation of the phosphodiesterase does not require the prior binding of cyclic GMP to the phosphodiesterase, and that alkaline phosphatase can reverse the protein kinase A-dependent activation of phosphodiesterase activity. Zaprinast is a mixed inhibitor of non-activated cyclic GMP phosphodiesterase activity. However, inhibition of the protein kinase A-activated phosphodiesterase is competitive. These results suggest that protein kinase A can modulate the inhibitory effects of zaprinast via perturbations of a non-catalytic binding site.
Original languageEnglish
Pages (from-to)1389-1396
Number of pages8
JournalBiochemical and Biophysical Research Communications
Volume189
Issue number3
DOIs
Publication statusPublished - 30 Dec 1992

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Cyclic AMP-Dependent Protein Kinase Catalytic Subunits
Cyclic GMP
Phosphoric Diester Hydrolases
Binding Sites
Modulation
Cyclic AMP-Dependent Protein Kinases
Lung
Chemical activation
Labeling
Alkaline Phosphatase

Keywords

  • 3',5'-cyclic-GMP phosphodiesterases
  • alkaline phosphatase
  • animals
  • cyclic GMP
  • enzyme activation
  • guinea pigs
  • isoenzymes
  • kinetics
  • lung
  • macromolecular substances
  • protein kinases
  • purinones
  • pyrazines
  • pyrrolidinones
  • rolipram

Cite this

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title = "Interaction of the catalytic subunit of protein kinase A with the lung type V cyclic GMP phosphodiesterase: modulation of non-catalytic binding sites",
abstract = "We have previously demonstrated that the catalytic sub-unit of protein kinase A can catalyse a potent activation of partially purified Type V cyclic GMP-specific phosphodiesterase activity (Burns et al., 1992, Biochem. J. 283, 487-491). We now demonstrate that this phosphodiesterase most likely has a sub-unit mass of 90kDa, based upon 32P-cyclic GMP photo-affinity labelling, that activation of the phosphodiesterase does not require the prior binding of cyclic GMP to the phosphodiesterase, and that alkaline phosphatase can reverse the protein kinase A-dependent activation of phosphodiesterase activity. Zaprinast is a mixed inhibitor of non-activated cyclic GMP phosphodiesterase activity. However, inhibition of the protein kinase A-activated phosphodiesterase is competitive. These results suggest that protein kinase A can modulate the inhibitory effects of zaprinast via perturbations of a non-catalytic binding site.",
keywords = "3',5'-cyclic-GMP phosphodiesterases, alkaline phosphatase, animals, cyclic GMP, enzyme activation, guinea pigs, isoenzymes, kinetics, lung, macromolecular substances, protein kinases, purinones, pyrazines, pyrrolidinones, rolipram",
author = "F Burns and Pyne, {N J}",
year = "1992",
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TY - JOUR

T1 - Interaction of the catalytic subunit of protein kinase A with the lung type V cyclic GMP phosphodiesterase

T2 - modulation of non-catalytic binding sites

AU - Burns, F

AU - Pyne, N J

PY - 1992/12/30

Y1 - 1992/12/30

N2 - We have previously demonstrated that the catalytic sub-unit of protein kinase A can catalyse a potent activation of partially purified Type V cyclic GMP-specific phosphodiesterase activity (Burns et al., 1992, Biochem. J. 283, 487-491). We now demonstrate that this phosphodiesterase most likely has a sub-unit mass of 90kDa, based upon 32P-cyclic GMP photo-affinity labelling, that activation of the phosphodiesterase does not require the prior binding of cyclic GMP to the phosphodiesterase, and that alkaline phosphatase can reverse the protein kinase A-dependent activation of phosphodiesterase activity. Zaprinast is a mixed inhibitor of non-activated cyclic GMP phosphodiesterase activity. However, inhibition of the protein kinase A-activated phosphodiesterase is competitive. These results suggest that protein kinase A can modulate the inhibitory effects of zaprinast via perturbations of a non-catalytic binding site.

AB - We have previously demonstrated that the catalytic sub-unit of protein kinase A can catalyse a potent activation of partially purified Type V cyclic GMP-specific phosphodiesterase activity (Burns et al., 1992, Biochem. J. 283, 487-491). We now demonstrate that this phosphodiesterase most likely has a sub-unit mass of 90kDa, based upon 32P-cyclic GMP photo-affinity labelling, that activation of the phosphodiesterase does not require the prior binding of cyclic GMP to the phosphodiesterase, and that alkaline phosphatase can reverse the protein kinase A-dependent activation of phosphodiesterase activity. Zaprinast is a mixed inhibitor of non-activated cyclic GMP phosphodiesterase activity. However, inhibition of the protein kinase A-activated phosphodiesterase is competitive. These results suggest that protein kinase A can modulate the inhibitory effects of zaprinast via perturbations of a non-catalytic binding site.

KW - 3',5'-cyclic-GMP phosphodiesterases

KW - alkaline phosphatase

KW - animals

KW - cyclic GMP

KW - enzyme activation

KW - guinea pigs

KW - isoenzymes

KW - kinetics

KW - lung

KW - macromolecular substances

KW - protein kinases

KW - purinones

KW - pyrazines

KW - pyrrolidinones

KW - rolipram

U2 - 10.1016/0006-291X(92)90228-D

DO - 10.1016/0006-291X(92)90228-D

M3 - Article

VL - 189

SP - 1389

EP - 1396

JO - Biochemical and Biophysical Research Communications

JF - Biochemical and Biophysical Research Communications

SN - 1090-2104

IS - 3

ER -