Role of Cyclic-AMP-Dependent Protein Kinase in the Regulation of Cellular Processes

  • Edwin G. Krebs
  • Donald K. Blumenthal
  • Arthur M. Edelman
  • C. Nicholas Hales
Part of the New Horizons in Therapeutics book series (NHTH)


Approximately 15 years ago it was shown that the stimulatory effect of cAMP on the phosphorylase kinase activation reaction in vitro was mediated by a distinct cAMP-dependent protein kinase, which exhibited broader specificity than that of a phosphorylase kinase kinase in that it could also catalyze the phosphorylation of casein and protamine (Walsh et al., 1968). Huijing and Larner (1966) had also concluded that the target for cAMP-mediated regulation of glycogen synthase was probably the synthase kinase itself, and a few years later it was determined that an identical cAMP-dependent protein kinase is involved in the phosphorylase kinase and glycogen synthase phosphorylation reactions (Schlender et al., 1969; Soderling et al., 1970). Noting a widespread distribution of the newly discovered cAMP-dependent protein kinase in various cell types and tissues, Kuo and Greengard (1969) postulated that all of the actions of cAMP are mediated by this enzyme. This hypothesis is still considered valid for most, if not all, eucaryotic cell functions controlled by cAMP, but it does not hold for procaryotes, in which the cAMP receptor protein, CRP (CAP), binds to DNA and regulates the catabolite-repressible operons (Pastan and Adhya, 1976).


Tyrosine Hydroxylase Cyclic Nucleotide Dependent Protein Kinase Dibutyryl cAMP Phosphorylase Kinase 
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  1. Adams, W. B., and Levitan, I. B., 1982, Intracellular injection of protein kinase inhibitor blocks the serotonin-induced increase in K+ conductance in Aplysia neuron R15, Proc. Natl. Acad. Sci. U.S.A. 79: 3877–3880.PubMedGoogle Scholar
  2. Adelstein, R. S., and Klee, C. B., 1981, Purification and characterization of smooth muscle myosin light chain kinase, J. Biol. Chem. 256: 7501–7509.PubMedGoogle Scholar
  3. Adelstein, R. S., Conti, M. A., Hathaway, D. R., and Klee, C. B., 1978, Phosphorylation of smooth muscle myosin light chain kinase by the catalytic subunit of adenosine 3’:5’- monophosphate-dependent protein kinase, J. Biol. Chem. 253: 8347–8350.PubMedGoogle Scholar
  4. Adelstein, R. S., Pato, M. D., and Conti, M. A., 1981, The role of phosphorylation in regulating contractile proteins, Adv. Cyclic Nucleotide Res. 14: 361–373.PubMedGoogle Scholar
  5. Alkon, D. L., Acosta-Urquidi, J., Olds, J., Kuzma, G., and Neary, J. T., 1983, Protein kinase injection reduces voltage-dependent potassium currents, Science 219: 303–306.PubMedGoogle Scholar
  6. Alousi, A., and Weiner, N., 1966, The regulation of norepinephrine synthesis in sympathetic nerves: Effect of nerve stimulation, cocaine and catecholamine-releasing agents, Proc. Natl. Acad. Sci. U.S.A. 56: 1491–1496.PubMedGoogle Scholar
  7. Andersson, R., Nilsson, K., Wikberg, J., Johansson, S., Mohme-Lundholm, E., and Lundholm, L., 1975, Cyclic nucleotides and the contraction of smooth muscle, Adv. Cyclic Nucleotide Res. 5: 491 - 518.PubMedGoogle Scholar
  8. Andrews, D. W., Langan, T. A., and Weiner, N., 1983, Evidence for the involvement of a cyclic AMP-independent protein kinase in the activation of soluble tyrosine hydroxylase from rat striatum, Proc. Natl. Acad. Sci. U.S.A. 80: 2097–2101.PubMedGoogle Scholar
  9. Beavo, J. A., Bechtel, P. J., and Krebs, E. G., 1974, Activation of protein kinase by physiological concentrations of cyclic AMP, Proc. Natl. Acad. Sci. U.S.A. 71: 3580–3583.PubMedGoogle Scholar
  10. Berkowitz, B. A., Tarver, J. H., and Spector, S., 1970, Release of norepinephrine in the central nervous system by theophylline and caffeine, Eur. J. Pharmacol. 10: 64–71.PubMedGoogle Scholar
  11. Boney, C., Fink, D. Schlichter, D., Carr, K., and Wicks, W. D., 1983, Direct evidence that the protein kinase catalytic subunit mediates the effects of cAMP on tyrosine aminotransferase synthesis, J. Biol. Chem. 258: 4911–4918.PubMedGoogle Scholar
  12. Boynton, A. L., and Whitfield, J. F., 1983, The role of cyclic AMP in cell proliferation: A critical assessment of the evidence, Adv. Cyclic Nucleotide Res. 15: 193–294.Google Scholar
  13. Bridenbaugh, R. L., Hoar, P. E., and Kerrick, W. G. L., 1981, Phosphorylation of myosin light chain kinase by C-subunit and its effects on smooth muscle, Biophys. J. 33: 235a.Google Scholar
  14. Brunelli, M., Castellucci, V., and Kandel, E. R., 1976, Synaptic facilitation and behavioral sensitization in Aplysia: Possible role of serotonin and cyclic AMP, Science 194: 1178–1181.PubMedGoogle Scholar
  15. Buxton, I. L. O., and Brunton, L. L., 1983, Compartments of cyclic AMP and protein kinase in mammalian cardiomyocytes, J. Biol. Chem. 258: 10233–10239.PubMedGoogle Scholar
  16. Carlson, G. M., and Graves, D. J., 1976, Stimulation of phosphorylase kinase autophosphorylation by peptide analogs of phosphorylase, J. Biol. Chem. 251: 7480–7486.PubMedGoogle Scholar
  17. Carlson, G. M., Bechtel, P. J., and Graves, D. J., 1979, Chemical and regulatory properties of phosphorylase kinase and cyclic AMP-dependent protein kinase, Adv. Enzymol. 50: 41–115.PubMedGoogle Scholar
  18. Castellucci, V. F., Kandel, E. R., Schwartz, J. H., Wilson, F. D., Nairn, A. C., and Greengard, P., 1980, Intracellular injection of the catalytic subunit of cyclic AMP-dependent protein kinase simulates facilitation of transmitter release underlying behavioral sensitization in Aplysia, Proc. Natl. Acad. Sci. USA. 77: 7492–7496.PubMedGoogle Scholar
  19. Castellucci, V. F., Nairn, A., Greengard, P., Schwartz, J. H., and Kandel, E. R., 1982, Inhibitor of adenosine 3’:5’-monophosphate-dependent protein kinase blocks presynaptic facilitation in Aplysia, J. Neurosci. 2: 1673–1681.PubMedGoogle Scholar
  20. Cedar, H., Kandel, E. R., and Schwartz, J. H., 1972, Cyclic adenosine monophosphate in the nervous system of Aplysia californica I. Increased synthesis in response to synaptic stimulation, J. Gen. Physiol. 60: 558–569.PubMedGoogle Scholar
  21. Chalfie, M., Settipani, L., and Perlman, R. L., 1979, The role of adenosine 3’:5’-mono-phosphate in the regulation of tyrosine 3-monooxygenase activity, Mol. Pharmacol. 15: 263–270.PubMedGoogle Scholar
  22. Chieuh, C. C., and Moore, K. E., 1974, In vivo release of endogenously synthesized catecholamines from the rat brain evoked by electrical stimulation and by d-amphetamine, J. Neurochem. 23: 159–168.Google Scholar
  23. Chrapkiewics, N. B., Beale, E. G., and Granner, D. K., 1982, Induction of the messenger ribonucleic acid coding for phosphoenolpyruvate carboxykinase in H4-II-E cells, J. Biol. Chem. 257: 14428–14432.Google Scholar
  24. Cohen, P., 1973, The subunit structure of rabbit skeletal muscle phosphorylase kinase and the molecular basis of its activation reactions, Eur. J. Biochem. 34: 1–14.PubMedGoogle Scholar
  25. Cohen, P., Watson, D. C., and Dixon, G. H., 1975, The hormonal control of activity of skeletal muscle phosphorylase kinase, Eur. J. Biochem. 51: 79–92.PubMedGoogle Scholar
  26. Cohen, P., Burchell, A., Foulkes, J. G., Cohen, P. T. W., Vanaman, T. C., and Nairn, A. C., 1978, Identification of the Ca2+-dependent modulator protein as the fourth subunit of rabbit skeletal muscle phosphorylase kinase, FEBS Lett. 92: 287–292.PubMedGoogle Scholar
  27. Conti, M. A., and Adelstein, R. S., 1981, The relationship between calmodulin binding and phosphorylation of smooth muscle myosin kinase by the catalytic subunit of 3’:5’ cAMP-dependent protein kinase, J. Biol. Chem. 256: 3178–3181.PubMedGoogle Scholar
  28. Corbin, J. D., 1983, Determination of the cAMP-dependent protein kinase activity ratio in intact tissues, Methods Enzymol. 99: 227–232.PubMedGoogle Scholar
  29. Corbin, J. D., Soderling, T. R., and Park, C. R., 1973, Regulation of adenosine 3’,5’-monophosphate-dependent protein kinase. 1. Preliminary characterization of the adipose tissue enzyme in crude extracts, J. Biol. Chem. 248: 1813–1821.PubMedGoogle Scholar
  30. Corbin, J. D., Sugden, P. H., Lincoln, T. M., and Keely, S. L., 1977, Compartmentalization of adenosine 3’: 5’-monophosphate and adenosine 3’:5’-monophosphate-dependent protein kinase in heart tissue, J. Biol. Chem. 252: 3854–3861.PubMedGoogle Scholar
  31. Culpepper, J. A., and Liu, A. Y.-C., 1983, Pretranslational control of tyrosine aminotransferase synthesis by 8-bromo-cyclic AMP in H-4 rat hepatoma cells, J. Biol. Chem. 258: 13812–13819.PubMedGoogle Scholar
  32. Dabrowska, R., Sherry, J. M. F., Aromatorio, D. K., and Hartshorne, D. J., 1978, Modulator protein as a component of the myosin light chain kinase from chicken gizzard, Biochemistry 17: 253–258.PubMedGoogle Scholar
  33. De Belleroche, J. S., Das, I., and Bradford, H. F., 1974, Absence of an effect of histamine, noradrenaline and depolarizing agents on the levels of adenosine 3’-5’-monophosphate in nerve endings isolated from cerebral cortex, Biochem. Pharmacol. 23: 835–843.PubMedGoogle Scholar
  34. de Lanerolle, P., Nishikawa, M., and Adelstein, R. S., 1983, Protein phosphorylation and cAMP-levels in forskolin-treated tracheal smooth muscle, Biophys. J. 41: 152a.Google Scholar
  35. Diamond, J., 1978, Role of cyclic nucleotides in control of smooth muscle contraction, Adv. Cyclic Nucleotide Res. 9: 327–339.PubMedGoogle Scholar
  36. Drummond, G. I., Harwood, J. P., and Powell, C. A., 1969, Studies on the activation of phosphorylase in skeletal muscle by contraction and by epinephrine, J. Biol. Chem. 214: 4235–4240.Google Scholar
  37. Ebstein, B., Roberge, C., Tabachnick, J., and Goldstein, M., 1974, The effect of dopamine and apomorphine on db-cAMP-induced stimulation of synaptosomal tyrosine hydroxylase, J. Pharm. Pharmacol. 26: 975–977.PubMedGoogle Scholar
  38. Edelman, A. M., Raese, J. D., Lazar, M. A., and Barchas, J. D., 1978, In vitro phosphor-ylation of a purified preparation of bovine corpus striatal tyrosine hydroxylase, Commun. Psychopharmacol. 2: 461–465.PubMedGoogle Scholar
  39. Edelman, A. M., Raese, J. D., Lazar, M. A., and Barchas, J. D., 1981, Tyrosine hydroxylase: Studies on the phosphorylation of a purified preparation of the brain enzyme by the cyclic AMP-dependent protein kinase, J. Pharmacol. Exp. Ther. 216: 647–653.PubMedGoogle Scholar
  40. El-Maghrabi, M. R., Claus, T. H., and Pilkis, S. J., 1983, Substrate-directed regulation of cAMP-dependent phosphorylation, Methods Enzymol. 99: 581–591.Google Scholar
  41. El-Mestikawy, S., Glowinski, J., and Hamon, M., 1983, Tyrosine hydroxylase activation in depolarized dopaminergic terminals—involvement of Ca2+-dependent phosphorylation, Nature 302: 830–833.PubMedGoogle Scholar
  42. Engstrom, L., 1980, Regulation of liver pyruvate kinase by phosphorylation-dephosphorylation, in: Molecular Aspects of Cellular Regulations, Vol. 1 ( P. Cohen, ed.), Elsevier/ North-Holland Biomedical Press, Amsterdam, pp. 11–31.Google Scholar
  43. Foerder, C. A., Martins, T. J., Beavo, J. A., Krebs, E. G., 1982, Induction of Xenopus laevis oocyte maturation by cyclic GMP-stimulated phosphodiesterase, J. Cell. Biol. 95: 304a.Google Scholar
  44. Frye, R. A., and Holz, R. W., 1983, Phospholipase A2 inhibitors block catecholamine secretion and calcium uptake in cultured bovine adrenal medullary cells, Mol. Pharmacol. 23: 547–550.PubMedGoogle Scholar
  45. Gerthoffer, W. T., and Murphy, R. A., 1983, Ca2+, myosin phosphorylation, and relaxation of arterial smooth muscle, Am. J. Physiol. 245: C271–C277.PubMedGoogle Scholar
  46. Gerthoffer, W. T., Trevethick, M. A., and Murphy, R. A., 1984, Myosin phosphorylation and cyclic adenosine 3’,5’-monophosphate in relaxation of arterial smooth muscle by vasodilators, Circ. Res. 54: 83–89.PubMedGoogle Scholar
  47. Goldstein, M., Anagnoste, B., and Shirron, C., 1973, The effect of trivastal, haloperidol and dibutyryl cyclic AMP on [14C]dopamine synthesis in rat striatum, J. Pharm. Pharmacol. 25: 348–351.PubMedGoogle Scholar
  48. Goldstein, M., Bronaugh, R. L., Ebstein, B., and Roberge, C., 1976, Stimulation of tyrosine hydroxylase activity by cyclic AMP in synaptosomes and in soluble striatal enzyme preparations, Brain Res. 109: 563–574.PubMedGoogle Scholar
  49. Gordon, R., Reid, J. V. O., Sjoerdsma, A., and Udenfriend, S., 1966, Increased synthesis in the rat heart on electrical stimulation of the stellate ganglia, Mol. Pharmacol. 2: 610–613.PubMedGoogle Scholar
  50. Gross, S. R., and Mayer, S. E., 1974, Regulation of phosphorylase b to a conversion in muscle, Life Sci. 14: 401–414.PubMedGoogle Scholar
  51. Hallenbeck, P. C., and Walsh, D. A., 1983, Autophosphorylation of phosphorylase kinase: Divalent metal cation and nucleotide dependency, J. Biol. Chem. 258: 13493–13501.PubMedGoogle Scholar
  52. Harper, J. F., Wallace, R. W., Cheung, W. Y., and Steiner, A. L., 1981, ACTH-stimulated changes in the immunocytochemical localization of cyclic nucleotides, protein kinases and calmodulin, Adv. Cyclic Nucleotide Res. 14: 581–591.PubMedGoogle Scholar
  53. Harris, J. E., and Roth, R. H., 1971, Potassium-induced acceleration of catecholamine biosynthesis in brain slices. 1. A study on the mechanism of action, Mol. Pharmacol. 7: 593–604.PubMedGoogle Scholar
  54. Harris, J. E., Morgenroth, V. H. III, Roth, R. H., and Baldessarini, R. J., 1974, Regulation of catecholamine synthesis in the rat brain in vitro by cyclic AMP, Nature 252: 156–158.PubMedGoogle Scholar
  55. Hayakawa, T., Perkins, J. P., and Krebs, E. G., 1973a, Studies on the subunit structure of rabbit skeletal muscle phosphorylase kinase, Biochemistry 12: 574–580.PubMedGoogle Scholar
  56. Hayakawa, T., Perkins, J. P., Walsh, D. A., and Krebs, E. G., 1973b, Physicochemical properties of rabbit skeletal muscle phosphorylase kinase, Biochemistry 12:567-573.Google Scholar
  57. Hayakawa, T., Perkins, J. P., Walsh, D. A., and Krebs, E. G., 1973b, Physicochemical properties of rabbit skeletal muscle phosphorylase kinase, Biochemistry 12: 567–573.PubMedGoogle Scholar
  58. Haycock, J. W., Bennett, W. F., George, R. J., and Waymire, J. C., 1982a, Multiple site phosphorylation of tyrosine hydroxylase: Differential regulation in situ by 8-bromo- cAMP and acetylcholine, J. Biol. Chem. 257: 13699–13703.PubMedGoogle Scholar
  59. Haycock, J. W., Meligeni, J. A., Bennett, W. F., and Waymire, J. C., 1982b, Phosphorylation and activation of tyrosine hydroxylase mediate the acetylcholine-induced increase in catecholamine biosynthesis in adrenal chromaffin cells, J. Biol. Chem. 257: 12641–12648.PubMedGoogle Scholar
  60. Hayes, J. S., Brunton, L. L., and Mayer, S. E., 1980, Selective activation of particulate cAMP-dependent protein kinase by isoproterenol and prostaglandin E1, J. Biol. Chem. 255: 5113–5119.PubMedGoogle Scholar
  61. Horwitz, J., and Perlman, R. L., 1984, Stimulation of DOPA synthesis in the superior cer-vical ganglion by veratridine, J. Neurochem. 42: 384–389.PubMedGoogle Scholar
  62. Huchon, D., Ozon, R., Fischer, E. H., and DeMaille, J. G., 1981, The pure inhibitor of cAMP-dependent protein kinase initiates Xenopus leavis meiotic maturation: A 4-step scheme for meiotic maturation, Mol. Cell. Endocrinol. 22: 211–222.PubMedGoogle Scholar
  63. Huijing, F., and Larner, J., 1966, On the effect of adenosine 3’,5’cyclophosphate on the kinase of UDGP a-l,4-glucan a-4-glucosyl transferase, Biochem. Biophys. Res. Commun. 23: 259–263.PubMedGoogle Scholar
  64. Iuvone, P. M., and Marshburn, P. B., 1982, Regulation of tyrosine hydroxylase activity in retinal cell suspensions: Effects of potassium and 8-bromo-cyclic AMP, Life Sci. 30: 85–91.PubMedGoogle Scholar
  65. Iuvone, P. M., Joh, T. H., and Neff, N. H., 1979, Regulation of retinal tyrosine hydroxylase: Long term exposure to light increased the apparent Vmax without a concomitant increase of immunotitratable enzyme molecules, Brain. Res. 178: 191–195.PubMedGoogle Scholar
  66. Iuvone, P. M., Rauch, A. L., Marshburn, P. B., Glass, D. B., and Neff, N. H., 1982, Activation of retinal tyrosine hydroxylase in vitro by cyclic AMP-dependent protein kinase: Characterization and comparison to activation in vivo by photic stimulation, J. Neurochem. 39: 1632–1640.PubMedGoogle Scholar
  67. Joh, T. H., Park, D. H., and Reis, D. J., 1978, Direct phosphorylation of brain tyrosine hydroxylase by cyclic AMP-dependent protein kinase: Mechanism of enzyme activation, Proc. Natl. Acad. Sci. U.S.A. 75: 4744–4748.PubMedGoogle Scholar
  68. Jones, L. R., Maddock, S. W., and Besch, H. R., 1980, Unmasking effect of alamethicin on the (Na+,K+)-ATPase, β-adrenergic receptor-coupled adenylate cyclase, and cAMP-dependent protein kinase activities of cardiac sarcolemmal vesicles, J. Biol. Chem. 255: 9971–9980.PubMedGoogle Scholar
  69. Jungmann, R. A., Lee, S. G., and DeAngelo, A. B., 1975, Translocation of cytoplasmic protein kinase and cyclic adenosine monophosphate-binding protein to intracellular acceptor sites, Adv. Cyclic Nucleotide Res. 5: 281–306.PubMedGoogle Scholar
  70. Kaczmarek, L., Jennings, K., Strumwasser, F., Nairn, A., Walter, U., Wilson, F., and Greengard, P., 1980, Microinjection of catalytic subunit of cyclic AMP-dependent protein kinase enhances calcium action potentials of bag cell neurons in cell culture, Proc. Natl. Acad. Sci. U.S.A. 77: 7487–7491.PubMedGoogle Scholar
  71. Kakiuchi, S., Rail, T. W., and Mcllwain, H., 1969, The effect of electrical stimulation upon the accumulation of adenosine 3’:5’-phosphate in isolated cerebral tissue, J. Neurochem. 16: 485–491.PubMedGoogle Scholar
  72. Kandel, E. R., and Schwartz, J. H., 1982, Molecular biology of learning: Modulation of transmitter release, Science 218: 433–443.PubMedGoogle Scholar
  73. Keely, S. L., Corbin, J. D., and Park, C. R., 1975, Regulation of adenosine 3’:5’-mono-phosphate-dependent protein kinase. Regulation of the heart enzyme by epinephrine, glucagon, insulin and l-methyl-3-isobutylxanthine, J. Biol. Chem. 250: 4832–4840.PubMedGoogle Scholar
  74. Keen, P., and McLean, W. G., Effect of dibutyryl-cyclic AMP and dexamethasone on noradrenaline synthesis in isolated superior cervical ganglia, J. Neurochem. 22: 5–10.Google Scholar
  75. Kerrick, W. G. L., and Bourguignon, L. Y. W., 1984, Regulation of receptor capping in mouse lymphoma T cells by CA2+-activated myosin light chain kinase, Proc. Natl. Acad. Sci. U.S.A. 81: 165–169.PubMedGoogle Scholar
  76. Kerrick, W. G. L., and Hoar, P. E., 1981, Inhibition of smooth muscle tension by cyclic AMP-dependent protein kinase, Nature 292: 253–255.PubMedGoogle Scholar
  77. Kerrick, W. G. L., Hoar, P. E., Cassidy, P. S., and Bridenbaugh, R. L., 1981, Skinned muscle fibers: Functional significance of phosphorylation and calcium activated tension, in: Protein Phosphorylation: Cold Spring Harbor Conferences on Cell Proliferation, Vol. 8 ( O. M. Rosen and E. G. Krebs, Eds.), Cold Spring Harbor Laboratory, Cold Spring Harbor, New York, pp. 887–900.Google Scholar
  78. Khoo, J. C., Sperry, P. J., Gill, G. N., and Steinberg, D., 1977, Activation of hormone-sensitive lipase and phosphorylase kinase by purified cyclic GMP-dependent protein kinase, Proc. Natl. Acad. Sci. U.S.A. 74: 4843–4847.PubMedGoogle Scholar
  79. King, M. M., Fitzgerald, T. J., and Carlson, G. M., 1983, Characterization of initial autophosphorylation events in rabbit skeletal muscle phosphorylase kinase, J. Biol. Chem. 258: 9925–9930.PubMedGoogle Scholar
  80. Krebs, E. G., 1973, The mechanism of hormonal regulation by cyclic AMP, Excerpta Medica Int. Cong. Ser. 273: 17–29.Google Scholar
  81. Krebs, E. G., and Beavo, J. A., 1979, Phosphorylation-dephosphorylation of enzymes, Annu. Rev. Biochem. 48: 923–959.PubMedGoogle Scholar
  82. Krebs, E. G., and Preiss, J., 1976, Regulatory mechanisms in glycogen metabolism, in: Biochemistry of Carbohydrates, Biochemistry Ser. 1, Vol. 5 ( W. J. Whelan, ed.), Butterworths-University Park Press, Baltimore, pp. 337–389.Google Scholar
  83. Krebs, E. G., DeLange, R. J., Kemp, R. G., and Riley, W. D., 1966, Activation of skeletal muscle phosphorylase, Pharmacol. Rev. 18: 163–171.PubMedGoogle Scholar
  84. Kuo, J. F., and Greengard, P., 1969, An adenosine 3’,5’-monophosphate-dependent protein kinase from Escherichia coli, J. Biol. Chem. 244: 3417–3419.PubMedGoogle Scholar
  85. Langan, T. A., Zeilig, C., and Leichtling, B., 1981, Characterization of multiple-site phosphorylation of HI histone in proliferating cells, in: Protein Phosphorylation: Cold Spring Harbor Conferences on Cell Proliferation, Vol. 8 ( O. M. Rosen and E. G. Krebs, eds.), Cold Spring Harbor Laboratory, Cold Spring Harbor, New York, pp. 1039–1052.Google Scholar
  86. Lazar, M. A., Truscott, R. J. W., Raese, J. D., and Barchas, J. D., 1981, Thermal denaturation of native striatal tyrosine hydroxylase: Increased thermolability of the phosphorylated form of the enzyme, J. Neurochem. 36: 677–682.PubMedGoogle Scholar
  87. Lazar, M. A., Lockfeld, A. J., Truscott, R. J. W., and Barchas, J. D., 1982, Tyrosine hydroxylase from bovine striatum: Catalytic properties of the phosphorylated and non- phosphorylated forms of the purified enzyme, J. Neurochem. 39: 409–442.PubMedGoogle Scholar
  88. Lee, S., and Jungmann, R. A., 1981, Isoproterenol-induced selective phosphorylation in vivo of the 214,000 dalton subunit of rat C6 glioma cell RNA polymerase II, Biochem. Biophys. Res. Commun. 102: 538–544.PubMedGoogle Scholar
  89. Letendre, C. H., MacDonnell, P. C., and Guroff, G., 1977, The biosynthesis of phospho¬rylated tyrosine hydroxylase by organ cultures of rat adrenal medulla and superior cervical ganglia, Biochem. Biophys. Res. Commun. 74: 891–897.PubMedGoogle Scholar
  90. Levitt, M., Spector, S., Sjoerdsma, A., and Udenfriend, S., 1965, Elucidation of the ratelimiting step in norepinephrine biosynthesis in the perfused guinea-pig heart, J. Pharmacol. Exp. Ther. 148: 1–8.PubMedGoogle Scholar
  91. Lewander, T., Joh, T. H., and Reis, D. J., 1977, Tyrosine hydroxylase: Delayed activation in central noradrenergic neurons and induction in adrenal medulla elicited by stimulation of central cholinergic receptors, J. Pharmacol. Exp. Ther. 200: 523–534.PubMedGoogle Scholar
  92. Lewis, E. J., Calie, P., and Wicks, W. D., 1982, Differences in rates of tyrosine aminotransferase deinduction with cyclic AMP and glucocorticoids, Proc. Natl. Acad. Sci. U.S.A. 79: 5778–5782.PubMedGoogle Scholar
  93. Lincoln, T. M., and Corbin, J. D., 1977, Adenosine 3’:5’-cyclic monophosphate- and guanosine 3’: 5’-cyclic monophosphate-dependent protein kinases: Possible homologous proteins, Proc. Natl. Acad. Sci. U.S.A. 74: 3239–3243.PubMedGoogle Scholar
  94. Lloyd, T., and Kaufman, S., 1975, Evidence for the lack of direct phosphorylation of bovine caudate tyrosine hydroxylase following activation by exposure to enzymatic phosphorylating conditions, Biochem. Biophys. Res. Commun. 66: 907–913.PubMedGoogle Scholar
  95. Lovenberg, W., Bruckwick, E. A., and Hanbauer, I., 1975, ATP, cyclic AMP and magnesium increase the affinity of rat striatal tyrosine hydroxylase for its cofactor, Proc. Natl. Acad. Sci. U.S.A. 72: 2955–2958.PubMedGoogle Scholar
  96. Maller, J. L., 1983, Interaction of steroids with the cyclic nucleotide system in amphibian oocytes, Adv. Cyclic Nucleotide Res. 15: 295–336.Google Scholar
  97. Maller, J. L., and Krebs, E. G., 1977, Progesterone-stimulated meiotic cell division in Xenopus oocytes: Induction by regulatory subunit and inhibition by catalytic subunit of adenosine 3’:5’-monophosphate-dependent protein kinase, J. Biol. Chem. 252: 1712–1718.PubMedGoogle Scholar
  98. Manning, D. R., DiSalvo, J., and Stull, J. T., 1980, Protein phosphorylation: Quantitative analysis in vivo and in intact cell systems, Mol. Cell. Endocrinol. 19: 1–19.PubMedGoogle Scholar
  99. Markey, K. A., Kondo, S., Shenkman, L., and Goldstein, M., 1980, Purification and characterization of tyrosine hydroxylase from a clonal pheochromocytoma cell line, Mol. Pharmacol. 17: 79–85.PubMedGoogle Scholar
  100. Masserano, J., and Weiner, N., 1979, Similarities between the in vivoactivation of adrenal tyrosine hydroxylase and thein vitroactivation of the enzyme by an adenosine 3’,5’- monophosphate dependent protein phosphorylating system, in:Catecholamines: Basic and Clinical Frontiers, Vol. 1 ( E. Usdin, I.J. Kopin, and J. D. Barchas, eds.), Pergamon Press, New York, pp. 100–102.Google Scholar
  101. Masserano, J. M., and Wiener, N., 1983, Tyrosine hydroxylase regulation in the central nervous system, Mol. Cell. Biochem. 53/54: 129–152.Google Scholar
  102. Mayer, S. E., and Krebs, E. G., 1970, Studies on the phosphorylation and activation of skeletal muscle phosphorylase and phosphorylase kinase in vivo, J. Biol. Chem. 245: 3153–3160.PubMedGoogle Scholar
  103. Meligeni, J., Tank, A. W., Stephens, J. K., Dreyer, E., and Weiner, N., 1981, In vivo phosphorylation of rat adrenal tyrosine hydroxylase during acute decapitation stress, in: Protein Phosporylation: Cold Spring Harbor Conferences on Cell Proliferation, Vol. 8 ( O. M. Rosenthal and E.G. Krebs, ed.), Cold Spring Harbor Laboratory, Cold Spring Harbor, New York, pp. 1377–1389.Google Scholar
  104. Meligeni, J. A., Haycock, J. W., Bennett, W. F., and Waymire, J. C., 1982, Phosphorylation and activation of tyrosine hydroxylase mediate the cAMP-induced increase in catecholamine biosynthesis in adrenal chromaffin cells, J. Biol. Chem. 257: 12632–12640.PubMedGoogle Scholar
  105. Miller, J. R., Silver, P. J., and Stull, J. T., 1983, The role of myosin light chain kinase phosphorylation in beta-adrenergic relaxation of tracheal smooth muscle, Mol. Pharmacol. 24: 235–242.PubMedGoogle Scholar
  106. Miller, P., Walter, U., Theurkauf, W. E., Vallee, R. B., and DeCamili, P., 1982, Frozen tissue sections as an experimental system to reveal specific binding sites for the regulatory subunit of type II cAMP-dependent protein kinase in neurons, Proc. Natl. Acad. Sci. U.S.A. 79: 5562–5566.PubMedGoogle Scholar
  107. Miyamoto, E., Petzold, G. L., Harris, J. S., and Greengard, P., 1971, Dissociation and concomitant activation of adenosine 3’,5’-monophosphate-dependent protein kinase by histone, Biochem. Biophys. Res. Commun. 44: 305–312.PubMedGoogle Scholar
  108. Morgenroth, V. H. III, Boadle-Biber, M., and Roth, R. H., 1974, Tyrosine hydroxylase: Activation by nerve stimulation, Proc. Natl. Acad. Sci. U.S.A. 71: 4283–4287.PubMedGoogle Scholar
  109. Morgenroth, V. H. III, Hegstrand, L. R., Roth, R. H., and Greengard, P., 1975, Evidence for involvement of protein kinase in the activation by adenosine 3’: 5’-monophosphate of brain tyrosine 3-monooxygenase, J. Biol. Chem. 250: 1946–1948.PubMedGoogle Scholar
  110. Mrwa, U., Troschka, M., and Ruegg, J. C., 1979, Cyclic AMP-dependent inhibition of smooth muscle actomyosin, FEBS Lett. 107: 371–374.PubMedGoogle Scholar
  111. Murrin, L. C., Morgenroth, V. H. Ill, and Roth, R. H., 1976, Dopaminergic neurons: Effects of electrical stimulation on tyrosine hydroxylase, Mol. Pharmacol. 12: 1070–1081.PubMedGoogle Scholar
  112. Nagatsu, T., Levitt, M., and Udenfriend, S., 1964, Tyrosine hydroxylase, the initial step in norepinephrine biosynthesis, J. Biol. Chem. 239: 2910–2917.PubMedGoogle Scholar
  113. Nathanson, J. A., 1977, Cyclic nucleotides and nervous system function, Physiol. Rev. 57: 157–256.PubMedGoogle Scholar
  114. Nimmo, H. G., and Cohen, P., 1977, Hormonal control of protein phosphorylation, Adv. Cyclic Nucleotide Res. 8: 145–255.PubMedGoogle Scholar
  115. Nishizuka, Y., Takai, Y., Kishimoto, A., Hashimoto, E., Inoue, M., Yamamoto, M., Criss, W. E., and Kuroda, Y., 1978, A role of calcium in the activation of a new protein kinase system, Adv. Cyclic Nucleotide Res. 9: 209–220.Google Scholar
  116. Noguchi, T., Disterhaft, M., and Granner, D., 1982, Evidence for a dual effect of dibutyryl cyclic AMP on the synthesis of tyrosine amino transferase in rat liver, J. Biol. Chem. 257: 2386–2390.PubMedGoogle Scholar
  117. Ogreid, D., Doskeland, S. O., and Miller, J. P., 1983, Evidence that cyclic nucleotides activating rabbit muscle protein kinase I interact with both types of cAMP binding sites associated with the enzyme, J. Biol. Chem. 258: 1041–1049.PubMedGoogle Scholar
  118. Palmer, W. K., McPherson, J. M., and Walsh, D. A., 1980, Critical controls in the evaluation of cAMP-dependent protein kinase activity ratios as indices of hormonal action, J. Biol. Chem. 255: 2663–2666.PubMedGoogle Scholar
  119. Pastan, I., and Adhya, S., 1976, Cyclic adenosine 3’-5’-monophosphate in Escherichia coli, Bacteriol. Rev. 40: 527–551.PubMedGoogle Scholar
  120. Pato, M. D., and Adelstein, R. S., 1980, Dephosphorylation of the 20,000 dalton light chain of myosin by two different phosphatases from smooth muscle, J. Biol. Chem. 255: 6535–6538.PubMedGoogle Scholar
  121. Patrick, R. L., and Barchas, J. D., 1974, Stimulation of synaptosomal dopamine synthesis by veratridine, Nature 250: 737–739.PubMedGoogle Scholar
  122. Patrick, R. L., and Barchas, J. D., 1976, Dopamine synthesis in rat brain synaptosomes. II. Dibutyryl cyclic adenosine 3’:5’-monophosphoric acid and 6-methyltetrahydropter- ine-induced synthesis increases without an increase in endogenous dopamine release, J. Pharmacol. Exp. Ther. 197: 97–104.PubMedGoogle Scholar
  123. Pollock, R. J., Kapatos, G., and Kaufman, S., 1981, Effect of cyclic AMP-dependent protein phosphorylating conditions on the pH-dependent activity of tyrosine hydroxylase from beef and rat striata, J. Neurochem. 37: 855–860.PubMedGoogle Scholar
  124. Posner, J. B., Stern, R., and Krebs, E. G., 1965, Effects of electrical stimulation and epinephrine on muscle phosphorylase, phosphorylase b kinase, and adenosine-3’,5’-phosphate, J. Biol. Chem. 240: 982–985.PubMedGoogle Scholar
  125. Raese, J. D., Edelman, A. M., Makk, G., Bruckwick, E. A., Lovenberg, W., and Barchas, J. D., 1979, Brain striatal tyrosine hydroxylase: Activation of the enzyme by cyclic AMP-independent phosphorylation, Commun. Psychopharmacol. 3: 295–301.PubMedGoogle Scholar
  126. Reimann, E. M., Titani, K., Ericsson, L. H., Wade, R. D., Fischer, E. H., and Walsh, K. A., 1984, Homology of the γ subunit of phosphorylase b kinase with cAMP-dependent protein kinase, Biochemistry 23: 4185–4192.PubMedGoogle Scholar
  127. Riley, W. D., DeLange, R. J., Bratvold, G. E., and Krebs, E. G., 1968, Reversal of phosphorylase kinase activation, J. Biol. Chem. 243: 2209–2215.PubMedGoogle Scholar
  128. Robinson-Steiner, A. M., and Corbin, J. D., 1983, Probable involvement of both intrachain cAMP binding sites in activation of protein kinase, J. Biol. Chem. 258: 1032–1040.PubMedGoogle Scholar
  129. Robison, G. A., Butcher, R. W., and Sutherland, E. W., 1971, Cyclic AMP, Academic Press, New York, London.Google Scholar
  130. Rosenfield, M. G., and Barrieux, A., 1979, Regulation of protein synthesis by polypeptide hormones and cyclic AMP, Adv. Cyclic Nucleotide Res. 10: 205–264.Google Scholar
  131. Roth, R. H., Morgenroth, V. H. III, and Salzman, P. M., 1975, Tyrosine hydroxylase: Allosteric activation induced by stimulation of central noradrenergic neurons, Naunyn-Schmiedebergs Arch. Pharmacol. 289: 327–343.Google Scholar
  132. Ruegg, J. C., and Paul, R. J., 1982, Vascular smooth muscle: Calmodulin and cyclic AMP- dependent protein kinase alter calcium sensitivity in porcine carotid skinned fibers, Circ. Res. 50: 394–399.PubMedGoogle Scholar
  133. Schlegel, R. A., and Rechsteiner, M. D., 1978, Red cell-mediated microinjection of mar- comolecules into mammalian cells, in: Methods in Cell Biology, Vol. 20 ( D. M. Prescott, ed.), Academic Press, New York, pp. 341–354.Google Scholar
  134. Schlender, K. K., Wei, S. H., and Villar-Palasi, C., 1969, UDP-glucose:glycogen a-4-glu- cosyltransferase I kinase activity of purified muscle protein kinase: Cyclic nucleotide specificity, Biochim. Biophys. Acta 191: 272–278.PubMedGoogle Scholar
  135. Sedvall, G. C., and Kopin, I. J., 1967, Acceleration of norepinephrine synthesis in the rat submaxillary gland in vivo during sympathetic nerve stimulation, Life Sci. 6: 45–51.PubMedGoogle Scholar
  136. Siekierka, J., Manne, V., and Ochoa, S., 1984, Mechanism of translational control by partial phosphorylation of the a subunit of eukaryotic initiation factor 2, Proc. Natl. Acad. Sci. U.S.A. 81: 352–356.PubMedGoogle Scholar
  137. Silver, P. J., and DiSalvo, J. D., 1979, Adenosine 3’:5’-monophosphate-mediated inhibition of myosin light chain phosphorylation in bovine aortic actomyosin, J. Biol. Chem. 254: 9951–9954.PubMedGoogle Scholar
  138. Silver, P. J., and Stull, J. T., 1982, Regulation of myosin light chain and phosphorylase phosphorylation in tracheal smooth muscle, J. Biol. Chem. 257: 6145–6150.PubMedGoogle Scholar
  139. Simon, J. R., and Roth, R. H., 1979, Striatal tyrosine hydroxylase: Comparison of the activation produced by depolarization and dibutyryl-cAMP, Mol. Pharmacol. 16: 224–233.PubMedGoogle Scholar
  140. Singh, T. J., and Wang, J. H., 1977, Effect of Mg2+ concentration on the cAMP-dependent protein kinase-catalyzed activation of rabbit skeletal muscle phosphorylase kinase, J. Biol. Chem. 252: 625–632.PubMedGoogle Scholar
  141. Singh, T. J., Akatsuka, A., and Huang, K. P., 1982, Phosphorylation and activation of rabbit skeletal muscle phosphorylase kinase by a cyclic nucleotide- and Ca2+-independent protein kinase, J. Biol. Chem. 257: 13379–13384.PubMedGoogle Scholar
  142. Skuster, J. R., Chan, K. F. J., and Graves, D. J., 1980, Isolation and properties of the catalytically active 7 subunit of phosphorylase b kinase, J. Biol. Chem. 255: 2203–2210.PubMedGoogle Scholar
  143. Soderling, T. R., Hickenbottom, J. P., Reimann, E. M., Hunkeler, F. L., Walsh, D. A., and Krebs, E. G., 1970, Inactivation of glycogen synthetase and activation of phosphorylase kinase by muscle adenosine 3’,5’-monophosphate-dependent protein kinase, J. Biol. Chem. 245: 6317–6328.PubMedGoogle Scholar
  144. Stadtman, E. R., Chock, P. B., and Adler, S. P., 1976, Metabolic regulation of coupled covalent modification cascade systems, in: Metabolic Interconversion of Enzymes, 1975 (S. Shaltiel, ed.), Springer-Verlag, Berlin, Heidelberg, New York, pp. 142–149.Google Scholar
  145. Steiner, A. L., Koide, Y., Earp, H. S., Bechtel, P. J., and Beavo, J. A., 1978, Comparmentalization of cyclic nucleotides and cyclic AMP-dependent protein kinases in rat livers: Immunocytochemical demonstration, Adv. Cyclic Nucleotide Res. 9: 691–705.PubMedGoogle Scholar
  146. Stull, J. T., 1980, Phosphorylation of contractile proteins in relation to muscle function, Adv. Cyclic Nucleotide Res. 13: 39–93.PubMedGoogle Scholar
  147. Stull, J. T., and Mayer, S. E., 1971, Regulation of phosphorylase activation in skeletal muscle in vivo, J. Biol. Chem. 246: 5716–5723.PubMedGoogle Scholar
  148. Taneda, M., Izumi, F., and Oka, M., 1974, Effect of dibutyryl adenosine 3’,5’-monophos-phate on catecholamine synthesis in rat brain cortical slices and isolated vasa deferentia, Jpn. J. Pharmacol. 24: 934–936.PubMedGoogle Scholar
  149. Tao, M., 1972, Dissociation of rabbit red blood cell cyclic AMP-dependent protein kinase by protamine, Biochem. Biophys. Res. Commun. 46: 56–61.PubMedGoogle Scholar
  150. Ullmann, A., and Danchin, A., 1983, Role of cyclic AMP in bacteria, Adv. Cyclic Nucleotide Res. 15: 1–53.Google Scholar
  151. Vaccaro, K. K., Liang, B. T., Perelle, B. A., and Perlman, R. L., 1980, Tyrosine 3-mon- oxygenase regulates catecholamine synthesis in pheochromocytoma cells, J. Biol. Chem. 255: 6539–6541.PubMedGoogle Scholar
  152. Vallet, B., Molla, A., and Demaille, J. G., 1981, Cyclic adenosine 3’:5’-monophosphate- dependent regulation of purified bovine aortic calcium/calmodulin-dependent myosin light chain kinase, Biochim. Biophys. Acta 674: 256–264.Google Scholar
  153. Vrana, K. E., Allhiser, C. L., and Roskoski, R., 1981, Tyrosine hydroxylase activation and inactivation by protein phosphorylating conditions, J. Neurochem. 36: 92–100.PubMedGoogle Scholar
  154. Vulliet, P. R., Langan, T. A., and Weiner, N., 1980, Tyrosine hydroxylase: A substrate of cyclic AMP-dependent protein kinase, Proc. Natl. Acad. Sci. U.S.A. 77: 92–96.PubMedGoogle Scholar
  155. Waldeck, B., 1971, Some effects of caffeine and aminophylline on the turnover of catecholamines in the brain, J. Pharm. Pharmacol. 23: 824–830.PubMedGoogle Scholar
  156. Walsh, D. A., Perkins, J. P., and Krebs, E. G., 1968, An adenosine 3’-5’-monophosphate- dependent protein kinase from rabbit skeletal muscle, J. Biol. Chem. 243: 3763–3765.PubMedGoogle Scholar
  157. Wang, J. H., Stull, J. T., Huang, T. S., and Krebs, E. G., 1976, A study on the autoactivation of rabbit muscle phosphorylase kinase, J. Biol. Chem. 251: 4521–4527.PubMedGoogle Scholar
  158. Weber, I. T., Takio, K., Titani, K., and Steitz, T. A., 1982, The cAMP-binding domains of the regulatory subunit of cAMP-dependent protein kinase and the catabolite gene activator protein are homologous, Proc. Natl. Acad. Sci. U.S.A. 79: 7679–7683.PubMedGoogle Scholar
  159. Weiner, N., Lee, F.-L., Dreyer, E., and Barnes, E., 1978, The activation of tyrosine hydroxylase in noradrenergic neurons during acute nerve stimulation, Life Sci. 22: 1197–1216.PubMedGoogle Scholar
  160. Yamauchi, T., and Fujisawa, H., 1979a, In vitro phosphorylation of bovine adrenal tyrosine hydroxylase by adenosine 3’:5’-monophosphate-dependent protein kinase, J. Biol. Chem. 254: 503–507.PubMedGoogle Scholar
  161. Yamauchi, T., and Fujisawa, H., 1979b, Regulation of bovine adrenal tyrosine 3-monoox- ygenase phosphorylation-dephosphorylation reaction catalyzed by adenosine 3’: 5’- monophosphate dependent protein kinase and phosphoprotein phosphatase, J. Biol. Chem. 254: 6408–6413.PubMedGoogle Scholar
  162. Yamauchi, T., and Fujisawa, H., 1981, Tyrosine 3-monooxygenase is phosphorylated by Ca2+-calmodulin-dependent protein kinase, followed by activation by activator protein, Biochem. Biophys. Res. Commun. 100: 807–813.PubMedGoogle Scholar
  163. Yeaman, S. J., and Cohen, P., 1975, The hormonal control of activity of skeletal muscle phosphorylase kinase: Phosphorylation of the enzyme at two sites in vivo in response to adrenalin, Eur. J. Biochem. 51:93–104.PubMedGoogle Scholar

Copyright information

© Plenum Press, New York 1985

Authors and Affiliations

  • Edwin G. Krebs
    • 1
  • Donald K. Blumenthal
    • 1
  • Arthur M. Edelman
    • 1
  • C. Nicholas Hales
    • 1
  1. 1.Howard Hughes Medical Institute Laboratory, Department of PharmacologyUniversity of WashingtonSeattleUSA

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