Evidence for the Presence of Substrates for cGMP Dependent Protein Phosphorylation in Human Synaptosomal Membranes

  • D. H. Boehme
  • R. Kosecki
  • N. Marks
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 116)


Substantial evidence exists that cyclic nucleotide effects are mediated by specific (intracellular) protein kinases. Since biological regulatory agents can affect intracellular levels of cyclic nucleotides, it has been proposed that protein phosphorylation is a central mech anism mediating their actions and thereby involved in many aspects of cellular function (see WALSH, 1978) . Relevance to studies on changes in protein phosphorylation with age arise from findings that neurotransmitters have age-related effects on levels of cyclic nucleotides (SCHMIDT & THORNBERRY, 1978; SCHMIDT et al., 1978) coupled with observations that there are changes in synaptic function and morphology during senescence (WALKER & WALKER, 1973; CRAGG, 1975; MCGEER & MCGEER, 1975). At the present time very few studies exist on alterations in protein phosphorylation in synaptic membranes—the major target sites of neurotransmitter action (DAVIS, 1977; TRUEX et al., 1978; BOEHME et al., 1978).


Cyclic Nucleotide Synaptic Membrane cGMP Dependent Protein Kinase SYNAPTOSOMAL Membrane Dent Protein Kinase 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. BOEHME, D.H., DOSECKI, R. & MARKS, N. (1978) Protein phosphorylation in human synaptosomal membranes: evidence for the presence of cGMP-dependent protein kinases. Brain Res. Bull, 3, in press.Google Scholar
  2. CASANELLI, J.R., SCHLICHTER, D.J., WALTER, U. & GREENGARD, P. (197 8) Photoaffinity labelling of cGMP-dependent protein kinase from vascular smooth muscle. J. Biol. Chem. 253, 4771–4776.Google Scholar
  3. COTMAN, C.E. & MATTHEWS, D.W. (1971) Synaptic plasma mem branes from rat brain synaptosomes: isolation and partial characterizations. Biochem. Biophys. Acta 249, 380–403.PubMedCrossRefGoogle Scholar
  4. CRAGG, B.G. (1975) The density of synapses and neurons in normal mentally defective and aging human brains. Brain 98, 81–90.PubMedCrossRefGoogle Scholar
  5. DAVIS, L.G. (1977) The subcellular distribution of endogenously phosphorylated proteins from cerebral cortex of newborn rats. Proc. Soc. Neurosci. III, 103.Google Scholar
  6. DUNN, N.J., KAIBARA, K. & KARCZMAR, A.G. (1977) Direct postsynaptic membrane effect of dibutryl cyclic GMP on mammalian sympathetic neurons. Neur. Pharmacology 16, 715–717.Google Scholar
  7. GILL, G.N., WALTON, G.M. & SPERRY, P.J. (1977) cGMP-dependent protein kinase from bovine lung. J. Biol. Chem. 252, 6443–6449.PubMedGoogle Scholar
  8. GREENGARD, P. (1976) Possible role for cyclic nucleotides and phosphorylated membrane proteins in postsynaptic action of neurotransmitters. Nature 260, 101–107.PubMedCrossRefGoogle Scholar
  9. HASHIGUCHI, T., USHIYAMA, N.S., KOBAYASHI, H. & LIBET, B. (197 8) Does cyclic GMP mediate the slow excitatory synaptic potentials in sympathetic ganglia? Nature 271, 267–268.PubMedCrossRefGoogle Scholar
  10. HERNANDEZ, A.G. (197 4) Protein synthesis by synaptosomes from rat brain. Biochem. J. 142, 7–17.PubMedGoogle Scholar
  11. KATZ, J.B., CRATRAVAS, G.N., VALASES, C. & WRIGHT, S.J. (197 8) Morphine reduces cerebellar cGMP content and elevates CSF cGMP content in rhesus monkey. Life Sci. 22, 467–472.PubMedCrossRefGoogle Scholar
  12. KUNUNGO, M.S. & THAKUR, M.K. (1977) Phosphorylation of chromosomal proteins as a function of age and its modulation by Ca2+. Biochem. Biophys. Res. Commun. T9_ ,1031–1035.CrossRefGoogle Scholar
  13. KUO, J.F. (1975) Changes in relative levels of cGMP and cAMP-dependent protein kinase in lung, heart and brain of developing guinea pigs. Proc. Natl. Acad. Sci. 72, 2256–2259.PubMedCrossRefGoogle Scholar
  14. MALKINSON, A.M. (1977) Developmental changes in the cAMP dependent phosphorylation and dephosphorylation of a protein endogenous to murine brain and liver. Biochem. Biophys. Res. Commun. 78, 91–98.PubMedCrossRefGoogle Scholar
  15. MCGEER, E.G. & MCGEER, P.L. (1976) Neurotransmitter metabolism in the aging brain. In Aging, Vol. 3. Neurobiology of Aging, pp. 398–403. Raven Press, New York.Google Scholar
  16. RAM, J.L. & EHRLICH, Y.H. (1978) Cyclic GMP-stimulated phosphorylation on membrane bound proteins from nerve roots of Aplysia California, J. Neurochem. 30, 487–491.PubMedCrossRefGoogle Scholar
  17. RODNIGHT, R., REDDINGTON, M. & GORDON, J. (1975) Methods for studying protein phosphorylation in cerebral tissues. Res. Meth. Neurochem. 3, 325–367.CrossRefGoogle Scholar
  18. ROUTENBERG, A. & EHRLICH. Y.H. (19757 Endogenous phos phorylation of four cerebral cortical membrane proteins: role of cyclic nucleotides, ATP and divalent cations. Brain Res. 92, 415–430.CrossRefGoogle Scholar
  19. SCHMIDT, M.J., PALMER, G.C. & ROBISON, G.A. (1978) The cyclic nucleotide system in brain during development and aging. In Psychopharmacology and Aging (Eisdorfer, C. & Fann, W.E., eds.). Spectrum Press, New York.Google Scholar
  20. SCHMIDT, M.J. & THORNBERRY, J.F. (197 7) Cyclic AMP and cyclic GMP accumulation in vitro in brain regions of young, old and aged rats Brain Res. 139, 169–177.CrossRefGoogle Scholar
  21. SHOJI, M., PATRICK, J.G., TSE, J. & KUO, J.F. (1977) Studies on cGMP-dependent protein kinases from bovine aorta. J. Biol. Chem. 252, 4347–4353.PubMedGoogle Scholar
  22. SOIFER, D. (1975) Enzymatic activity in tubulin preparations: cAMP dependent protein kinase activity of brain microtubule protein. J. Neurochem. 24, 21–33.PubMedCrossRefGoogle Scholar
  23. TAKAI, Y., NISHIYAMI, K., JAMAMURA, H. & NISHIZUKA, Y. (197 5) cGMP-dependent protein kinase from bovine cerebellum. J. Biol. Chem. 250, 4690–4695.PubMedGoogle Scholar
  24. TERRY, R.D. & WISNIEWSKI, H.M. (1970) The ultrastructure of the neurofibriliary tangle and the senile plaque. In Ciba Fdn. Symposium on Alzheimer’s Disease and Related Conditions (Wolstenholme, G.E.W. & O’Connor, M., eds.), pp. 145–168. J & A Churchill, London.Google Scholar
  25. TRUEX, L ., CONWAY, A., ROUTENBERG, A. & SCHMIDT , M.J. (197 8) cAMP-dependent protein kinase and protein phosphorylation in human brain during aging. Proc. Soc. Neurosci. IV, 129.Google Scholar
  26. UEDA, T., MAENO, H. & GREENGARD, P. (197 3) Regulation of endogenous phosphorylation of specific proteins in synaptic membrane preparations from rat brain by cAMP. J. Biol. Chem. 248, 8295–8305.PubMedGoogle Scholar
  27. WALKER, J.B. St WALKER, J.P. (1973) Properties of adenylate cyclase from senescent rat brain. Brain Res. 54, 391–396.PubMedCrossRefGoogle Scholar
  28. WALSH, D.A. (1978) The role of the cAMP-dependent protein kinase as the transducer of cAMP action. Biochem. Pharmacol. 27, 1801–1804.PubMedCrossRefGoogle Scholar
  29. WIEGANT, V.M., ZWIERS, H., SCHOTMAN, P., GISPEN, W.H. (1978) Endogenous phosphorylation of rat brain synaptosomal plasma membranes in vitro; some methodological aspects. Neurochem. Res. 3, 443–454.PubMedCrossRefGoogle Scholar
  30. WILLIAMS, M. & RODNIGHT, R. (1977) Protein phosphorylation in nervous tissue: possible involvement in nervous tissue functions and relationship to cyclic nucleotide metabolism. Progress in Neurobiology 8 ,183–250.CrossRefGoogle Scholar

Copyright information

© Plenum Press, New York 1979

Authors and Affiliations

  • D. H. Boehme
    • 1
  • R. Kosecki
    • 1
  • N. Marks
    • 2
  1. 1.VA Medical CenterEast OrangeUSA
  2. 2.Center for NeurochemistryRockland Research InstituteWards IslandUSA

Personalised recommendations