Guanine Nucleotide Regulatory Proteins in Inflammatory and Immune Responses

  • Allen M. Spiegel
Part of the New Horizons in Therapeutics book series (NHTH)


Initially discovered in studies of hormone-regulated adenylate cyclase activity (Rodbell, 1980), guanine nucleotide regulatory proteins (G proteins) are now known to couple receptors for many different types of extracellular signals to several different types of effector. Recent evidence shows that G proteins are involved in transduction of inflammatory and immune response signals in neutrophils, macrophages, and lymphocytes. With the appreciation of the diversity of receptors and effectors coupled by G proteins has come an appreciation of the diversity of the G proteins themselves. At least five different G proteins have been identified to date and more will certainly be discovered. A distinctive form of G protein appears to be particularly abundant in neutrophils and possibly other leukocytes. Notwithstanding the diversity of G proteins, each member of this family of signal transducers shares certain common features. In this chapter, I will review these common features of G proteins, highlight specific aspects of G-protein structure and function, and review information on G proteins and the transduction of inflammatory and immune response signals.


Adenylate Cyclase Cholera Toxin Guanine Nucleotide Pertussis Toxin GTPase Activity 
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. Aksamit, R. R., Backlund, P. S., Jr., and Cantoni, G. L., 1985, Cholera toxin inhibits chemotaxis by a cAMP-independent mechanism, Proc. Natl. Acad. Sci. U.S.A. 82: 7475–7479.PubMedCrossRefGoogle Scholar
  2. Angus, C. W., Van Meurs, K. P., Tsai, S.-C., Adamik, R., Miedel, M. C., Pan, Y.-C. E., Kung, H.-F., Moss, J., and Vaughan, M., 1986, Identification of the probable site of choleragen-catalyzed ADP-ribosylation in a Goa-like protein based on cDNA sequence, Proc. Natl. Acad. Sci. U.S.A. 83: 5813–5816.PubMedCrossRefGoogle Scholar
  3. Backlund, P. S., Jr., Meade, B. D., Manclark, C. R., Cantoni, G. L., and Aksamit, R. R., 1985, Pertussis toxin inhibition of chemotaxis and the ADP-ribosylation of a membrane protein in a human—mouse hybrid cell line, Proc. Natl. Acad. Sci. U.S.A. 82: 2637–2641.PubMedCrossRefGoogle Scholar
  4. Barrowman, M. M., Cockroft, S., and Gomperts, B. D., 1986, Two roles for guanine nucleotides in the stimulus secretion sequence of neutrophils, Nature 319: 504–507.PubMedCrossRefGoogle Scholar
  5. Berridge, M. J., and Irvine, R. F., 1984, Inositol trisphosphate, a novel second messenger in signal transduction, Nature 312: 315–321.PubMedCrossRefGoogle Scholar
  6. Bigay, J., Deterre, P., Pfister, C., and Chabre, M., 1985, Fluoroaluminates activate transducin-GDP by mimicking the y-phosphate of GTP in its binding site, FEBS Lett. 191: 181–185.PubMedCrossRefGoogle Scholar
  7. Brandt, S. J., Dougherty, R. W., Lapetina, E. G., and Niedel, J. E., 1985, Pertussis toxin inhibits chemotactic peptide-stimulated generation of inositol phosphates and lysosomal enzyme secretion in human leukemic (HL60) cells, Proc. Natl. Acad. Sci. U.S.A. 82: 3277–3280.PubMedCrossRefGoogle Scholar
  8. Bray, P., Carter, A., Simons, C., Guo, V., Pucket, C., Kamholtz, J., Spiegel, A., and Nirenberg, M., 1986, Human cDNA clones for four species of G-a signal transduction protein, Proc. Natl. Acad. Sci. U.S.A. 83: 8893–8897.PubMedCrossRefGoogle Scholar
  9. Bray, P., Carter, A., Spiegel, A., and Nirenberg, M., 1987, Human cDNA clone for brain Gia, Proc. Natl. Acad. Sci. U.S.A. 84: 5115–5119.PubMedCrossRefGoogle Scholar
  10. Cassel, D., and Pfeuffer, T., 1978, Mechanism of cholera toxin action: Covalent modification of the guanyl nucleotide-binding protein of the adenylate cyclase system, Proc. Natl. Acad. Sci. U.S.A. 75: 2669–2673.PubMedCrossRefGoogle Scholar
  11. Cassel, D., and Selinger, Z., 1977, Mechanism of adenylate cyclase activation by cholera toxin: Inhibition of GTP hydrolysis at the regulatory site, Proc. Natl. Acad. Sci. U.S.A. 74: 3307–3311.PubMedCrossRefGoogle Scholar
  12. Cerione, R. A., Staniszewski, C., Benovic, J. L., Lefkowitz, R. J., Caron, M. F., Gierschik, P., Somers, R., Spiegel, A. M., Codina, J., and Bimbaumer, L., 1985, Specificity of the functional interactions of the ß-adrenergic receptor and rhodopsin with guanine nucleotide regulatory proteins reconstituted in phospholipid vesicles, J. Biol. Chem. 260: 1493–1500.PubMedGoogle Scholar
  13. Cerione, R. A., Staniszewski, C., Gierschik, P., Codina, J., Somers, R. L., Bimbaumer, L., Spiegel, A. M., Caron, M. G., and Lefkowitz, R. J., 1986a, Mechanism of guanine nucleotide regulatory protein-mediated inhibition of adenylate cyclase, J. Biol. Chem. 261: 9514–9520.PubMedGoogle Scholar
  14. Cerione, R. A., Regan, J. W., Nakata, H., Codina, J., Benovic, J. L., Gierschik, P., Somers, R. L., Spiegel, A. M., Bimbaumer, L., Lefkowitz, R. J., and Caron, M. G., 1986b, Functional reconstitution of the a-adrenergic receptor with guanine nucleotide regulatory proteins in phospholipid vesicles, J. Biol. Chem. 261: 3901–3909.PubMedGoogle Scholar
  15. Cockcroft, S., and Gomperts, B. D., 1985, Role of guanine nucleotide binding protein in the activation of polyphosphoinositide phosphodiesterase, Nature 314: 534–536.PubMedCrossRefGoogle Scholar
  16. Codina, J., Hildebrandt, J., Iyengar, R., Bimbaumer, L., Sekura, R. D., and Manclark, C. R., 1983, Pertussis toxin substrate, the putative N, component of adenylyl cyclases, is an a-ß heterodimer regulated by guanine nucleotide and magnesium, Proc. Natl. Acad. Sci. U.S.A. 80: 4276–4280.PubMedCrossRefGoogle Scholar
  17. Codina, J., Stengel, D., Woo, S., and Bimbaumer, L., 1986, 0-Subunits of the human liver GS/G; signal-transducing proteins and those of bovine retinal rod cell transducin are identical, FEBS Lett. 207: 187–193.Google Scholar
  18. Darner, F. J., Mahan, L. C., Koachman, A. M., and Insel, P. A., 1982, Stimulation by forskolin of intact S49 lymphoma cells involves the nucleotide regulatory protein of adenylate cyclase, J. Biol. Chem. 256: 11901–11907.Google Scholar
  19. Didsbury, J. R., Ho, Y. S., and Snyderman, R., 1987, Human G, protein a-subunit: Deduction of amino acid structure from a cloned cDNA, FEBS Lett. 211: 160–164.PubMedCrossRefGoogle Scholar
  20. Dixon, R. A. F., Kobilka, B. K., Strader, D. J., Benovic, J. L., Dohlman, H. G., Frielle, T., Bolanowski, M. A., Bennett, C. D., Rands, E., Diehl, R. E., Mumford, R. A., Slater, E. E., Sigal, I. S., Caron, M. G., Lefkowitz, R. J., and Strader, C. D., 1986, Cloning of the gene and cDNA for mammalian 0-adrenergic receptor and homology with rhodopsin, Nature 321: 75–79.PubMedCrossRefGoogle Scholar
  21. Evans, S. W., Beckner, S. K., and Farrar, W. L., 1987, Stimulation of specific GTP binding and hydrolysis activities in lymphocyte membrane by interleukin-2, Nature 325: 166–168.PubMedCrossRefGoogle Scholar
  22. Falloon, J., Malech, H., Milligan, G., Unson, C., Kahn, R., Goldsmith, P., and Spiegel, A., 1986, Detection of the major pertussis toxin substrate of human leukocytes with antisera raised against synthetic peptides, FEBS Lett. 209: 352–356.PubMedCrossRefGoogle Scholar
  23. Ferguson, K. M., Higashijima, T., Smigel, M. D., and Gilman, A. G., 1986, The influence of bound GDP on the kinetics of guanine nucleotide binding to G proteins, J. Biol. Chem. 261: 7393–7399.PubMedGoogle Scholar
  24. Florio, V. A., and Stemweis, P. C., 1985, Reconstitution of resolved muscarinic cholinertic receptors with purified GTP-binding proteins, J. Biol. Chem. 260: 3477–3483.PubMedGoogle Scholar
  25. Fung, B. K.-K., 1983, Characterization of transducin from bovine retinal rod outer segments. I. Separation and reconstitution of the subunits, J. Biol. Chem. 258: 10495–10502.PubMedGoogle Scholar
  26. Gibbs, J. B., Sigal, I. S., Poe, M., and Scolnick, E. M., 1984, Intrinsic GTPase activity distinguishes normal and oncogenic ras p21 molecules, Proc. Natl. Acad. Sci. U.S.A. 81: 5704–5708.PubMedCrossRefGoogle Scholar
  27. Gierschik, P., Codina, J., Simons, C., Birnbaumer, L., and Spiegel, A., 1985, Antisera against a guanine nucleotide binding protein from retina cross-react with the 13 subunit of the adenylyl cyclase associated guanine nucleotide binding proteins, NS and Ni, Proc. Natl. Acad. Sci. U.S.A. 82: 727–731.PubMedCrossRefGoogle Scholar
  28. Gierschik, P., Falloon, J., Milligan, G., Pines, M., Gallin, J. I., and Spiegel, A., 1986a, Immunochemical evidence for a novel pertussis toxin substrate in human neutrophils, J. Biol. Chem. 261: 8058–8062.PubMedGoogle Scholar
  29. Gierschik, P., Milligan, G., Pines, M., Goldsmith, P., Codina, J., Klee, W., and Spiegel, A., 1986b, Use of specific antibodies to quantitate the guanine nucleotide-binding protein Go in brain, Proc. Natl. Acad. Sci. U.S.A. 83: 2258–2262.PubMedCrossRefGoogle Scholar
  30. Gierschik, P., Sidiropoulos, D. Spiegel, A. and Jakobs, K. H., 1987, Purification and characterization of the major pertussis toxin-sensitive guanine nucleotide-binding protein of bovine neutrophil membranes, Eur. J., Biochem. 165: 185–194.CrossRefGoogle Scholar
  31. Gill, D. M. and Meren, H., 1978, ADP-ribosylation of membrane proteins catalysed by cholera toxin: Basis of the activaiton of adenylate cyclase, Proc. Natl. Acad. Sci. U.S.A. 75: 305–3054.CrossRefGoogle Scholar
  32. Gilman. A. G., 1984. G proteins and dual control of adenylate cyclase, Cell 36: 577–579.PubMedCrossRefGoogle Scholar
  33. Goldman, D. W. Chang. F. H., Gifford, L. A., Goetz, E. J. and Bourne, H. R. 1985. Pertussis toxin inhibition of chemotactic factor-induced calcium mobilization and function in human polymorphonuclear leukocytes, J. Exp. Med. 162: 145–156.PubMedCrossRefGoogle Scholar
  34. Halliday, K., 1984, Regional homology in GTP-binding proto-oncogene products and elongation factors, J. Cyclic Nucleotide Protein Phosphor. Res. 9: 43548.Google Scholar
  35. Harris, B. A., Robishaw, J. D., Mumby, S. M., and Gilman, A. G., 1985, Molecular cloning of complementary DNA of the a subunit of the G protein that stimulates adenylate cyclase, Science 229: 1274–1277.PubMedCrossRefGoogle Scholar
  36. Hescheler, J., Rosenthal, W. Trautwein, W., and Schultz, G., 1987, The GTP-binding protein, Go, regulates neuronal calcium channels, Nature 325: 445–447.PubMedCrossRefGoogle Scholar
  37. Hildebrandt, J. D., Hanoune, J., and Birnbaumer, L., 1982, Guanine nucleotide inhibition of cyc-$49 mouse lymphoma cell membrane adenylyl cyclase, J. Biol. Chem. 257: 14723–14725.PubMedGoogle Scholar
  38. Hildebrandt, J. D., Codina, J., Rosenthal, W., Birnbaumer, L., Neer, E. J., Yamazaki, A. and Bitensky, M. W., 1985, Characterization by two-dimensional peptide mapping of the y subunits of Ns and Ni, the regulatory proteins of adenylate cyclase, and of transducin, the guanine nucleotide-binding protein of rod outer segments of the eye, J. Biol. Chem. 260: 14867–14872.PubMedGoogle Scholar
  39. Hinkle, P. M., and Phillips, W. J., 1984, Thyrotropin-releasing hormone stimulates GTP hydrolysis by membranes from GH4C1 rat pituitary tumor cells, Proc. Natl. Acad. Sci. U.S.A. 81: 6183–6187.PubMedCrossRefGoogle Scholar
  40. Hsia, J. A., Moss, J., Hewlett, E. L., and Vaughan, M., 1984, ADP-ribosylation of adenylate cyclase by pertussis toxin, J. Biol. Chem. 259: 1086–1090.PubMedGoogle Scholar
  41. Huff, R. M., Axton, J. M., and Neer, E. G., 1985, Physical and immunological characterization of a guanine nucleotide-binding protein purified from bovine cerebral cortex, J. Biol. Chem. 260: 10864–10871.PubMedGoogle Scholar
  42. Hurley, J. B., Simon, M. I., Teplow, D. B., Robishaw, J. D., and Gilman, A. G., 1984, Homologies between signal transducing G proteins and ras gene products, Science 226: 860–862.PubMedCrossRefGoogle Scholar
  43. Imboden, J. B., and Stobo, J. D., 1985, Transmembrane signaling by the T-cell antigen receptor, J. Exp. Med. 161: 446–456.PubMedCrossRefGoogle Scholar
  44. Imboden, J. B., Shoback, D. M., Pattison, G., and Stobo, J. D., 1986, Cholera toxin inhibits the T-cell antigen receptor-mediated increases in inositol trisphosphate and cytoplasmic free calcium, Proc. Natl. Acad. Sci. U.S.A. 83: 5673–5677.PubMedCrossRefGoogle Scholar
  45. Itoh, H., Kozasa, T., Nagata, S., Nakamura, S., Katada, T., Ui. M., Iwai, S., Ohtsuka, E., Kawasaki, H., Suzuki, K., and Kaziro, Y., 1986, Molecular cloning and sequence determination of cDNAs for a subunits of the guanine nucleotide-binding proteins Gs, G, and Go from rat brain, Proc. Natl. Acad. Sci. U.S.A. 83: 3776–3780.PubMedCrossRefGoogle Scholar
  46. Iyengar, R., and Bimbaumer, L., 1982, Hormone receptor modulates the regulatory component of adenylyl cyclase by reducing its requirement for Mg2+ and enhancing its extent of activation by guanine nucleotides, Proc. Natl. Acad. Sci. U.S.A. 79: 5179–5183.PubMedCrossRefGoogle Scholar
  47. Jakway, J. P., and DeFranco, A. L., 1986, Pertussis toxin inhibition of B cell and macrophage responses to bacterial lipopolysaccharide, Science 234: 743–746.PubMedCrossRefGoogle Scholar
  48. Johnson, G. L., Kaslow, H. R., and Bourne, H. R., 1978, Genetic evidence that cholera toxin substrates are regulatory components of adenylate cyclase, J. Biol. Chem. 253: 7120–7132.PubMedGoogle Scholar
  49. Jumak, F., 1985, Structure of the GDP domain of EF-Tu and location of the amino acids homologous to ras oncogene proteins, Science 230: 32–36.CrossRefGoogle Scholar
  50. Katada, T., Bokoch, G. M., Northup, J. K., Ui, M., and Gilman, A. G., 1984a, The inhibitory guanine nucleotide-binding regulatory component of adenylate cyclase. Properties and function of the purified protein, J. Biol. Chem. 259: 3568–3577.PubMedGoogle Scholar
  51. Katada, T., Northup, J. K., Bokoch, G. M., Ui, M., and Gilman, A. G., 1984b, The inhibitory guanine nucleotide-binding regulatory component of adenylate cyclase. Subunit dissociation and guanine nucleotide-dependent hormonal inhibition, J. Biol. Chem. 259: 3578–3585.PubMedGoogle Scholar
  52. Katada, T., Gilman, A. G., Watanabe, Y., Bauer, S., and Jakobs, K. H., 1985, Protein kinase C phosphorylates the inhibitory guanine nucleotide-binding regulatory component and apparently suppresses its function in hormonal inhibition of adenylate cyclase, Eur. J. Biochem. 151: 431–437.PubMedCrossRefGoogle Scholar
  53. Kikuchi, A., Kozawa, O., Kaibuchi, K., Katada, T., Ui, M., and Takai, Y., 1986, Direct evidence for involvement of a guanine nucleotide-binding protein in chemotactic peptide-stimulated formation of inositol bisphosphate and trisphosphate in differentiated human leukemic (HL-60) cells, J. Biol. Chem. 261: 11558–11562.PubMedGoogle Scholar
  54. Kubo, T., Fukuda, K., Mikami, A., Maeda, A., Takahashi, H., Mishina, M., Haga, T., Haga, K., Ichiyama, A., Kangawa, K., Kojima, M., Matsuo, Y., Hirose, T., and Numa, S., 1986, Cloning, sequencing and expression of complementary DNA encoding the muscarinic acetylcholine receptor, Nature 323: 411–416.PubMedCrossRefGoogle Scholar
  55. Lerea, C. L., Somers, D. E., Hurley, J. B., Klock, I. B., and Budt-Milan, A. H., 1986, Identification of specific transducin a subunits in retinal rod and cone photoreceptors, Science 234: 77–80.PubMedCrossRefGoogle Scholar
  56. Litosch, I., Wallis, C., and Fain, J. N., 1985, 5-Hydroxytryptamine stimulates inositol phosphate production in a cell-free system from blowfly salivary glands. Evidence for a role of GTP in coupling receptor activation to phosphoinositide breakdown, J. Biol. Chem. 260: 5464–5471.Google Scholar
  57. Lochrie, M.A., Hurley, J. B., and Simon, M. I., 1985, Sequence of the a subunit of photoreceptor G protein: Homologies between transducin, ras, and elongation factors, Science 228: 96–99.PubMedCrossRefGoogle Scholar
  58. Logothetis, D. E., Kurachi, Y., Galper, J., Neer, E. J., and Clapham, D. E., 1987, The 13-y subunits of GTP-binding proteins activate the muscarinic K+ channel in heart, Nature 325: 321–326.PubMedCrossRefGoogle Scholar
  59. Madaule, P., and Axel, R., 1985, A novel ras-related gene family, Cell 41: 31–40.PubMedCrossRefGoogle Scholar
  60. Manning, D. R., and Gilman, A. G., 1983, The regulatory components of adenylate cyclase and transducin. A family of structure homologous guanine nucleotide binding proteins, J. Biol. Chem. 258: 7059–7063.PubMedGoogle Scholar
  61. Mattera, R., Codina, J., Crozat, A., Kidd, V., Woo, S. L. C., and Birnbaumer, L., 1986, Identification by molecular cloning of two forms of the a-subunit of the human liver stimulatory (Ga) regulatory component of adenylyl cyclase, FEBS Lett. 206: 36–41.PubMedCrossRefGoogle Scholar
  62. May, D. C., Ross, E. M., Gilman, A. G., and Smigel. M. D., 1985., Reconstitution of catecholamine-stimulated adenylate cyclase activity using three purified proteins, J. Biol. Chem. 260: 15829–15833.Google Scholar
  63. Medynski, D. C., Sullivan, K., Smith, D., Van Dop, C., Chang, F. H., Fung, B.K.-K., Seeburg, P. H., and Bourne, H. R., 1985, Amino acid sequence of the a subunit of transducin deduced from the cDNA sequence, Proc. Natl. Acad. Sci. U.S.A. 82: 4311–4315.PubMedCrossRefGoogle Scholar
  64. Mumby. S. M., Kahn, R. A., Manning, D. R., and Gilman, A. G., 1986, Antisera of designed specificity for subunits of guanine nucleotide-binding regulatory proteins, Proc. Natl. Acad. Sci. U.S.A. 83: 265–269.CrossRefGoogle Scholar
  65. Mustelin, T., Poso, H., and Andersson, L. C., 1986, Role of G-proteins in T-cell activation: Nonhydrolysable GTP analogues induce early ornithine decarboxylase activity in human T lymphocytes, EMBO J. 5: 3287–3290.PubMedGoogle Scholar
  66. Nakamura. T., and Ui, M., 1985, Simultaneous inhibitions of inositol phospholipid breakdown, arachidonic acid release, and histamine secretion in mast cells by islet-activating protein, pertussis toxin, J. Biol. Chem. 260: 3584–3593.Google Scholar
  67. Nathans, J., Thomas, D., and Hogness, D. S., 1986, Molecular genetics of human color vision: The genes encoding blue, green, and red pigments, Science 232: 193–202.PubMedCrossRefGoogle Scholar
  68. Neer, E. J., Lok, J.M. and Wolf, L. G., 1984, Purification and properties of the inhibitory guanine nucleotide regulatory unit of brain adenylate cyclase, J. Biol. Chem. 259: 14222–14229.PubMedGoogle Scholar
  69. Nukada, T., Tanabe, T., Takahashi, H., Noda, M., Hirose, T., lnayama, S., and Numa, S., 1986a, Primary structure of the a-subunit of bovine adenylate cyclase-stimulating G-protein deduced from the cDNA sequence, FEBS Lett. 195: 220–224.PubMedCrossRefGoogle Scholar
  70. Nukada, T., Tanabe, T., Takahashi, H., Noda, M., Haga, K., Haga, T., Ichiyama, A., Kangawa, K., Hiranaga, M., Matsuo, H., and Numa, S., 1986b, Primary structure of the a-subunit of bovine adenylate cyclase-inhibiting G-protein deduced from the cDNA sequence, FEBS Leu. 197: 305–310.CrossRefGoogle Scholar
  71. Okajima, Fumikazu, and Ui, M., 1984, ADP ribosylation of the specific membrane protein by islet-activating protein, pertussis toxin, associated with inhibition of a chemotactic peptide-induced arachidonate release in neutrophils, J. Biol. Chem. 259: 13863–13871.PubMedGoogle Scholar
  72. Owens, J. R., Frame, L. T., Ui, M., and Cooper, D. M. F., 1985, Cholera toxin ADPribosylates and islet-activating protein substrate in adipocyte membranes and alters its function, J. Biol. Chem. 260: 15946–15952.PubMedGoogle Scholar
  73. Pellman, D. Garber, E. A., Cross, F. R., and Hanafusa, H., 1985, An N-terminal peptide from p60src can direct myristylation and plasma membrane localization when fused to heterologous proteins, Nature 314: 374–377.PubMedCrossRefGoogle Scholar
  74. Pfeuffer, E., Dreher, R.-M., Metzger, H., and Pfeuffer, T., 1985, Catalytic unit of adenylate cyclase: Purification and identification by affinity crosslinking, Proc. Natl. Acad. Sci. U.S.A. 82: 3086–3090.PubMedCrossRefGoogle Scholar
  75. Robishaw, J. D., Smigel, M. D., and Gilman, A. G., 1986, Molecular basis for two forms of the G protein that stimulates adenylate cyclase, J. Biol. Chem. 261: 9587–9590.PubMedGoogle Scholar
  76. Rodbell, M., 1980, The role of hormone receptors and GTP-regulatory proteins in membrane transduction, Nature 284: 17–21.PubMedCrossRefGoogle Scholar
  77. Rodbell, M., 1985, Programmable messengers: A new theory of hormone action, Trends Biochem. Sci. 119: 461–464.CrossRefGoogle Scholar
  78. Roof, D. J., Applebury, M. L., and Sternweis, P. C., 1985, Relationships within the family of GTP-binding proteins isolated from bovine central nervous system, J. Biol. Chem. 260: 16242–16249.PubMedGoogle Scholar
  79. Ross, E. M., Howlett, A. C., Ferguson, K. M., and Gilman, A. G., 1978, Reconstitution of hormone-sensitive adenylate cyclase activity with resolved components of the enzyme, J. Biol. Chem. 253: 6401–6412.PubMedGoogle Scholar
  80. Seamon, K. B., Vaillancourt, R., Edwards, M., and Daly, J. W., 1984, Binding of [3H]forskolin to rat brain membranes, Proc. Natl. Acad. Sci. U.S.A. 81: 5081–5085.PubMedCrossRefGoogle Scholar
  81. Shinozawa, T., Uchida, S., Martin, E., Cafiso, D., Hubbell, W., and Bitensky, M., 1980, Additional Component required for activity and reconstitution of light-activated vertebrate photoreceptor GTPase, Proc. Natl. Acad. Sci. U.S.A. 77: 1408–1411.PubMedCrossRefGoogle Scholar
  82. Smith, C. D., Lane, B. C., Kusaka, I., Verghese, M. W., and Snyderman, R., 1985, Chemoattractant receptor-induced hydrolysis of phosphatidyl 4,5-bisphosphate in human polymorphonuclear leukocyte membranes. Requirement for a guanine nucleotide regulatory protein, J. Biol. Chem. 260: 5875–5878.PubMedGoogle Scholar
  83. Spiegel, A. M., 1987a, Signal transduction by guanine nucleotide binding protiens, Mol. Cell. Endocrinol. 49: 1–16.PubMedCrossRefGoogle Scholar
  84. Spiegel, A. M., 1987b Guanine nucleotide binding proteins and signal transduction, Vitam. Horm. 44 (in press).Google Scholar
  85. Spiegel, A. M., Gierschik, P., Levine, M. A., and Downs, R. W., Jr., 1985, Clinical implications of guanine nucleotide-binding proteins as receptor—effector couplers, N. Engl. J. Med. 312: 26–33.PubMedCrossRefGoogle Scholar
  86. Sternweis, P. C., 1985, The purified a subunits of Go and G, from bovine brain require ß-y for association with phospholipid vesicles, J. Biol. Chem. 261: 631–637.Google Scholar
  87. Sternweis, P. C., and Gilman, A. G., 1982, Aluminum: A requirement for activation of the regulatory component of adenylate cyclase by fluoride, Proc. Natl. Acad. Sci. U.S.A. 79: 4888–4891.PubMedCrossRefGoogle Scholar
  88. Sternweis, P. C., and Robishaw, J. D., 1984, Isolation of two proteins with high affinity for guanine nucleotides from membranes of bovine brain, J. Biol. Chem. 259: 13806–13813.PubMedGoogle Scholar
  89. Sternweis, P. C., Northup, J. K., Smigel, M. D., and Gilman, A. G., 1981, The regulatory component of adenylate cyclase, J. Biol. Chem. 256: 11517–11526.PubMedGoogle Scholar
  90. Stryer, L., 1986, Cyclic GMP cascade of vision, Annu. Rev. Neurosci. 9: 87–119.PubMedCrossRefGoogle Scholar
  91. Sullivan, K. A., Liao, Y.-C, Alborzi, A., Beiderman, B., Chang, F.-H., Masters, S. B., Levinson, A. D., and Bourne, H. R., 1986, Inhibitory and stimulatory G proteins of adenylate cyclase: cDNA and amino acid sequences of the a chains, Proc. Natl. Acad. Sci. U.S.A. 83: 6687–6691.PubMedCrossRefGoogle Scholar
  92. Tanabe, T., Nukada, T., Nishikawa, Yl, Sugimoto, K., Suzuki, H., Takahashi, H., Noda, M., Haga, T., Ichiyama, A., Kangawa, K., Minamino, N., Matsuo, H., and Numa, S., 1985, Primary structure of the a subunit of transducin and its relationship to ras proteins, Nature 315: 242–245.PubMedCrossRefGoogle Scholar
  93. Ui, M., 1984, Islet-activating protein, pertussis toxin: A probe for functions of the inhibitory guanine nucleotide regulatory component of adenylate cyclase, Trends Pharmacol. Sci. 5: 277–279.CrossRefGoogle Scholar
  94. Verghese, M. W., Fox, K., McPhail, L. C., and Snyderman, R., 1985, Chemoattractantelicited alterations of cAMP levels in human polymorphonuclear leukocytes require a CA++-dependent mechanism which is independent of transmembrane activation of adenylate cyclase, J. Biol. Chem. 260: 6769–6775.PubMedGoogle Scholar
  95. Verghese, M., Uhing, R. J., and Snyderman, R., 1986, A pertussis/cholera-toxin-sensitive N protein may mediate chemoattractant receptor signal transduction, Biochem. Biophys. Res. Commun. 138: 887–894.PubMedCrossRefGoogle Scholar
  96. West, R. E., Jr., Moss, J., Vaughan, M., Liu, T., and Liu, T.-Y., 1985, Pertussis toxincatalyzed ADP ribosylation of transducin. Cysteine 347 is the ADP-ribose acceptor site, J. Biol. Chem. 260: 14428–14430.PubMedGoogle Scholar
  97. Williamson, J. R., 1986, Role of inositol lipid breakdown in the generation of intracellular signals, Hypertension 8:11140–11156.Google Scholar
  98. Willumsen, B. M., Norris, K., Papageorge, A. G., Hubbert, N. L., and Lowy, D. R., 1984, Harvey murine sarcoma virus p21 ras protein: Biological and biochemical significance of the cysteine nearest the carboxy terminus, EMBO J. 3: 2581–2585.PubMedGoogle Scholar
  99. Yarden, Y., Rodriguez, H., Wong, S. K.-F., Brandt, D. R., May, D. C., Burnier, J., Harkins, R. N., Chen, E. Y., Ramachandran, J., Ullrich, A., and Ross, E. M., 1986, The avian ß-adrenergic receptor: Primary structure and membrane topology, Proc. Natl. Acad. Sci. U.S.A. 83: 6795–6799.PubMedCrossRefGoogle Scholar
  100. Yatani, A., Codina, J., Brown, A. M., and Birnaumer, L., 1987, Direct activation of mammalian atrial muscarinic potassium channels by GTP regulatory protein Gk, Science 235: 207–211.PubMedCrossRefGoogle Scholar
  101. Zick, Y., Eisenberg, R. S., Pines, M., Gierschik, P., and Spiegel, A. M., 1986, Multi-site phosphorylation of the et subunit of transducin by the insulin receptor kinase and protein kinase C, Proc. Natl. Acad. Sci. U.S.A. 83: 9294–9297.PubMedCrossRefGoogle Scholar

Copyright information

© Plenum Press, New York 1988

Authors and Affiliations

  • Allen M. Spiegel
    • 1
  1. 1.Molecular Pathophysiology Section, National Institute of Diabetes, Digestive, and Kidney DiseasesNational Institutes of HealthBethesdaUSA

Personalised recommendations