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. 1974 Oct;71(10):4037–4041. doi: 10.1073/pnas.71.10.4037

Guanosine 3′:5′-Monophosphate-Dependent Protein Kinases in Mammalian Tissues

J F Kuo 1
PMCID: PMC434323  PMID: 4372603

Abstract

The mammalian protein kinase activity stimulated preferentially by low concentrations of guanosine 3′:5′-monophosphate (cyclic GMP), but not by adenosine 3′:5′-monophosphate (cyclic AMP), was readily assayed in a modified incubation system that contained a neutral phosphate buffer, protein kinase modulator, and arginine-rich histone. Cyclic GMP-dependent protein kinase activity assayed under these conditions was about two to three orders of magnitude higher than that previously detected. The enzyme activity occurred in all guinea pig and rat tissues (lung, heart, aorta, brain, liver, ileum, adipose, and pancreatic islets) examined. The activity can be separated from the cyclic AMP-dependent protein kinase activity, also present in the same tissues, by means of either Sephadex G-200 gel filtration or ammonium sulfate fractionation. The cyclic GMP-dependent enzyme preparations had Ka values for cyclic GMP ranging from 0.03 to 0.12 μM, compared to the Ka values for cyclic AMP ranging from 0.6 to 3.8 μM. The presence of phosphate and protein kinase modulator was essential for maximal cyclic GMP-dependent enzyme activity.

The occurrence of high levels of cyclic GMP-dependent protein kinase activity in mammalian tissues clearly suggests that it may serve as a “target” enzyme for cyclic GMP, mediating many biological effects of this cyclic nucleotide.

Keywords: cyclic AMP, protein kinase modulator

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Appleman M. M., Birnbaumer L., Torres H. N. Factors affecting the activity of muscle glycogen synthetase. 3. The reaction with adenosine triphosphate Mg++, and cyclic 3'5'-adenosine monophosphate. Arch Biochem Biophys. 1966 Sep 26;116(1):39–43. doi: 10.1016/0003-9861(66)90009-9. [DOI] [PubMed] [Google Scholar]
  2. Casnellie J. E., Greengard P. Guanosine 3':5'-cyclic monophosphate-dependent phosphorylation of endogenous substrate proteins in membranes of mammalian smooth muscle. Proc Natl Acad Sci U S A. 1974 May;71(5):1891–1895. doi: 10.1073/pnas.71.5.1891. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Donnelly T. E., Jr, Kuo J. F., Reyes P. L., Liu Y. P., Greengard P. Protein kinase modulator from lobster tail muscle. I. Stimulatory and inhibitory effects of the modulator on the phosphorylation of substrate proteins by guanosine 3',5'-monophosphate-dependent and adenosine 3',5'-monophosphate-dependent protein kinases. J Biol Chem. 1973 Jan 10;248(1):190–198. [PubMed] [Google Scholar]
  4. Ferrendelli J. A., Steiner A. L., McDougal D. B., Jr, Kipnis D. M. The effect of oxotremorine and atropine on cGMP and cAMP levels in mouse cerebral cortex and cerebellum. Biochem Biophys Res Commun. 1970 Nov 25;41(4):1061–1067. doi: 10.1016/0006-291x(70)90193-2. [DOI] [PubMed] [Google Scholar]
  5. George W. J., Polson J. B., O'Toole A. G., Goldberg N. D. Elevation of guanosine 3',5'-cyclic phosphate in rat heart after perfusion with acetylcholine. Proc Natl Acad Sci U S A. 1970 Jun;66(2):398–403. doi: 10.1073/pnas.66.2.398. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Goldberg N. D., Dietz S. B., O'Toole A. G. Cyclic guanosine 3',5'-monophosphate in mammalian tissues and urine. J Biol Chem. 1969 Aug 25;244(16):4458–4466. [PubMed] [Google Scholar]
  7. Hardman J. G., Davis J. W., Sutherland E. W. Effects of some hormonal and other factors on the excretion of guanosine 3',5'-monophosphate and adenosine 3',5'-monophosphate in rat urine. J Biol Chem. 1969 Dec 10;244(23):6354–6362. [PubMed] [Google Scholar]
  8. Hofmann F., Sold G. A protein kinase activity from rat cerebellum stimulated by guanosine-3':5'-monophosphate. Biochem Biophys Res Commun. 1972 Nov 15;49(4):1100–1107. doi: 10.1016/0006-291x(72)90326-9. [DOI] [PubMed] [Google Scholar]
  9. Illiano G., Tell G. P., Siegel M. E., Cuatrecasas P. Guanosine 3':5'-cyclic monophosphate and the action of insulin and acetylcholine. Proc Natl Acad Sci U S A. 1973 Aug;70(8):2443–2447. doi: 10.1073/pnas.70.8.2443. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Kuo J. F., Greengard P. Cyclic nucleotide-dependent protein kinases. IV. Widespread occurrence of adenosine 3',5'-monophosphate-dependent protein kinase in various tissues and phyla of the animal kingdom. Proc Natl Acad Sci U S A. 1969 Dec;64(4):1349–1355. doi: 10.1073/pnas.64.4.1349. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Kuo J. F., Greengard P. Cyclic nucleotide-dependent protein kinases. VI. Isolation and partial purification of a protein kinase activated by guanosine 3',5'-monophosphate. J Biol Chem. 1970 May 25;245(10):2493–2498. [PubMed] [Google Scholar]
  12. Kuo J. F., Kuo W. N. Regulation by beta-adrenergic receptor and muscarinic cholinergic receptor activation of intracellular cyclic AMP and cyclic GMP levels in rat lung slices. Biochem Biophys Res Commun. 1973 Dec 10;55(3):660–665. doi: 10.1016/0006-291x(73)91195-9. [DOI] [PubMed] [Google Scholar]
  13. Kuo J. F., Lee T. P., Reyes P. L., Walton K. G., Donnelly T. E., Jr, Greengard P. Cyclic nucleotide-dependent protein kinases. X. An assay method for the measurement of quanosine 3',5'-monophosphate in various biological materials and a study of agents regulating its levels in heart and brain. J Biol Chem. 1972 Jan 10;247(1):16–22. [PubMed] [Google Scholar]
  14. Kuo J. F., Miyamoto E., Reyes P. Activation and dissociation of adenosine 3'-5'-monophosphate-dependent and guanosine 3'-5'-monophosphate-dependent protein kinases by various cyclic nucleotide analogs. Biochem Pharmacol. 1974 Jul 15;23(14):2011–2021. doi: 10.1016/0006-2952(74)90260-3. [DOI] [PubMed] [Google Scholar]
  15. Kuo J. F., Wyatt G. R., Greengard P. Cyclic nucleotide-dependent protein kinases. IX. Partial purification and some properties of guanosine 3',5'-monophosphate-dependent and adenosine 3',5'-monophosphate-dependent protein kinases from various tissues and species of Arthropoda. J Biol Chem. 1971 Dec 10;246(23):7159–7167. [PubMed] [Google Scholar]
  16. Langan T. A. Histone phosphorylation: stimulation by adenosine 3',5'-monophosphate. Science. 1968 Nov 1;162(3853):579–580. doi: 10.1126/science.162.3853.579. [DOI] [PubMed] [Google Scholar]
  17. Miyamoto E., Kuo J. F., Greengard P. Cyclic nucleotide-dependent protein kinases. 3. Purification and properties of adenosine 3',5'-monophosphate-dependent protein kinase from bovine brain. J Biol Chem. 1969 Dec 10;244(23):6395–6402. [PubMed] [Google Scholar]
  18. Murad F., Manganiello V., Vaughan M. A simple, sensitive protein-binding assay for guanosine 3':5'-monophosphate. Proc Natl Acad Sci U S A. 1971 Apr;68(4):736–739. doi: 10.1073/pnas.68.4.736. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Walsh D. A., Ashby C. D., Gonzalez C., Calkins D., Fischer E. H. Krebs EG: Purification and characterization of a protein inhibitor of adenosine 3',5'-monophosphate-dependent protein kinases. J Biol Chem. 1971 Apr 10;246(7):1977–1985. [PubMed] [Google Scholar]
  20. Walsh D. A., Perkins J. P., Krebs E. G. An adenosine 3',5'-monophosphate-dependant protein kinase from rabbit skeletal muscle. J Biol Chem. 1968 Jul 10;243(13):3763–3765. [PubMed] [Google Scholar]

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