Agonist Receptors and G proteins as Mediators of Platelet Activation

  • Lawrence F. Brass
  • James A. Hoxie
  • Thomas Kieber-Emmons
  • David R. Manning
  • Mortimer Poncz
  • Marilyn Woolkalis
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 344)


Recent studies have helped to define the earliest events of signal transduction in platelets, particularly those involved in the generation of second messengers. The best-understood of these events are those which involve guanine nucleotide binding regulatory proteins. G proteins are heterotrimers comprised of α, β and γ subunits, each of which can exist in multiple forms. Some, but not all, of the known variants of Gα are substrates for ADP-ribosylation by pertussis toxin, a modification which disrupts the flow of information from receptor to effector. The G proteins that have been identified in platelets to date are Gs, Gi1, Gi2, Gi3, Gz and Gq. Gs and one or more of the Gi family members regulate cAMP formation by adenylylcyclase. Gi may also be responsible for the pertussis toxin-sensitive activation of phospholipase C which occurs when platelets are activated by thrombin. Gq is thought to be responsible for the pertussis toxin-resistant activation of phospholipase C by TxA2. Gz does not have an established role, but has the unique property of being phosphorylated by protein kinase C during platelet activation. Recent efforts to clone the receptors that interact with G proteins in platelets have been successful for epinephrine, thrombin, TxA2 and platelet activating factor. Each of these resembles other G protein-coupled receptors, being comprised of a single polypeptide with 7 transmembrane domains. In the case of thrombin, receptor activation is thought to involve a unique mechanism in which thrombin cleaves its receptor, creating a new N-terminus that can serve as a tethered ligand. Peptides corresponding to the tethered ligand can mimic the effects of thrombin, while antibodies to the same domain inhibit platelet activation. Shortly after activation, thrombin receptors become resistant to re-activation by thrombin. This desensitization, which appears to be due to a combination of proteolysis, phosphorylation and internalization, provides a potential mechanism for limiting the duration of thrombin-initiated signals in platelets.


Platelet Activation Human Platelet Pertussis Toxin Platelet Response Thrombin Receptor 
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  1. Amatruda, T.T. III., Steele, D.A., Slepak, V.Z., and Simon, M.I., 1991, Ga16, a G protein a subunit specifically expressed in hematopoietic cells, Proc Natl Acad Sci USA, 88:5587.PubMedCrossRefGoogle Scholar
  2. Benovic, J.L., Regan, J.W., Matsui, H., Mayor, F., Cotecchia, S., Leeb-Lundberg, L.M.F, Caron, M.G., and Lefkowitz, R.J., 1987, Agonist-dependent phosphorylation of the a2- adrenergic receptor by the Il-adrenergic receptor kinase, J Biol Chem, 262:17251.PubMedGoogle Scholar
  3. Blank, J.L.,Ross, A.H., and Exton, J.H., 1991, Purification and characterization of two G-proteins that activate the β1 isozyme of phosphoinositide-specific phospholipase C. Identification as members of the Gq class, J Biol Chem, 266:18206.PubMedGoogle Scholar
  4. Bouvier, M., Collins, S., O’Dowd, B.F., Campbell, P.T., Kobilka, B.K., MacGregor, C., Irons, G.P., Caron, M.G., and Lefkowitz, R.J., 1989, Two distinct pathways for cAMP-mediated down-regulation of the α2 adrenergic receptor: phosphorylation of the receptor and regulation of its mRNA level, J Biol Chem, 264:16786.PubMedGoogle Scholar
  5. Brass, L.F., Shaller, C.C., and Belmonte, E.J., 1987, Inositol 1,4,5-triphosphate-induced granule secretion in platelets. Evidence that the activation of phospholipase C mediated by platelet thromboxane receptors involves a guanine nucleotide binding protein-dependent mechanism distinct from that of thrombin, J Clin Invest,79:1269.PubMedCrossRefGoogle Scholar
  6. Brass, L.F., Woolkalis, M.J., and Manning, D.R., 1988, Interactions in platelets between G proteins and the agonists that stimulate phospholipase C and inhibit adenylyl cyclase, J Biol Chem, 263:5348.PubMedGoogle Scholar
  7. Brass, L.F., Manning, D.R., Williams, A., Woolkalis, M.J., and Poncz, M., 1991, Receptor and G proteinmediated responses to thrombin in HEL cells, J Biol Chem, 266:958.PubMedGoogle Scholar
  8. Brass, L.F., 1992, Homologous desensitization of HEL cell thrombin receptors:distinguishable roles for proteolysis and phosphorylation, J Biol Chem, 267:6044.PubMedGoogle Scholar
  9. Brass, L.F., Vassallo, R.R.,Jr., Belmonte, E., Ahuja, M., Cichowski, K., and Hoxie, J.A., 1992, Structure and function of the human platelet thrombin receptor: studies using monoclonal antibodies against a defined epitope within the receptor N-terminus, J Biol Chem, 267: 13795.PubMedGoogle Scholar
  10. Brass, L.F., and Woolkalis, M.J., 1992, Dual regulation of cAMP formation by thrombin in HEL cell, a leukemic cell line with megakaryocytic properties, Biochem J, 281:73.PubMedGoogle Scholar
  11. Burch, R.M., Luini, A., and Axelrod, J., 1986, Phospholipase A2 and phospholipase C are activated by distinct GTP-binding proteins in response to alpha 1-adrenergic stimulation in FRTL5 thyroid cells, Proc Natl Acad Sci USA, 83:7201.PubMedCrossRefGoogle Scholar
  12. Carey, F., Menashi, S., and Crawford, N., 1982, Localization of cyclo-oxygenase and thromboxane synthetase in human platelet intracellular membranes, Biochem J, 264:847.Google Scholar
  13. Carlson, K., Brass, L.F., and Manning, D.R., 1989, Thrombin and phorbol esters cause the selective phosphorylation of a G protein other than Gi in human platelets, J Biol Chem, 264:13298.PubMedGoogle Scholar
  14. Cichowski, K., McCormick, F., and Brugge, J.S., 1992, р21rasGAP association with fyn, lyn and yes in thrombin-activated platelets, J Biol Chem,267:5025.PubMedGoogle Scholar
  15. Coller, B.S., Springer, K.T., Scudder, L.E., and Norton, K.J., 1991, Studies of peptides derived from a platelet receptor, Blood,78(Suppl.1):394a.Google Scholar
  16. Coughlin, S.R., and Lingappa, V.R., 1989 Expression of a thrombin receptor in Xenopus oocytes, Clin Res 37:379A.Google Scholar
  17. De Marco, L., Mazzucato, M., Masotti, A., Fenton, J.W. II., and Ruggeri, Z.M., 1991), Function of glycoprotein Ibα in platelet activation induced by α-thrombin. J Biol Chem, 266:23776.PubMedGoogle Scholar
  18. Dennis, E.A., Rhee, S.G., Billah, M.M., and Hannun, Y.A., 1991, Role of phospholipases in generating lipid second messengers in signal transduction, FASER J, 5:2068.Google Scholar
  19. Ercolani, L., Stow, J.L., Boyle, J.F., Holtman, E.J., Lin, H., Grove, J.R., and Ausiello, D.A., 1990, Membrane localization of the pertussis toxin-sensitive G protein subunits αi2 and αi3 and expression of a metallothionein-αi2 fusion gene in LLC-PK1 cells, Proc Nall Acad Sci USA,87:4635.CrossRefGoogle Scholar
  20. Fischer, T.H., Galling, M.N., Lacal, J-C., and White, G.C.II., 1990, Rap1B, a cAMP-dependent protein kinase substrate, associates with the platelet cytoskeleton, J Biol Chem, 265:19405.PubMedGoogle Scholar
  21. Fox, J.E.B., Reynolds, C.C., and Johnson, M.M., 1987, Identification of glycoprotein Ibb as one of the major proteins phosphorylated during expsoure of intact platelets to agents that activate cAMPdependent protein kinase, J Biol Chem, 262:12627.PubMedGoogle Scholar
  22. Gagnon, A.W., Manning, D.R., Catani, L., Gewirtz, A., Poncz, M., and Brass, L.F., 1991, Identification of Gza as a pertussis toxin-insensitive G protein in human platelets and megakaryocytes, Blood, 78:1247.PubMedGoogle Scholar
  23. Gilman, A.G., 1987, G proteins: transducers of receptor-generated signals, Ann Rev Biochem,56:615.PubMedCrossRefGoogle Scholar
  24. Golden, A., and Brugge, J.S., 1989, Thrombin treatment induces rapid changes in tyrosine phosphorylation in platelets, Proc Nail Acad Sci USA, 86:901.CrossRefGoogle Scholar
  25. Greco, N.J., and Jamieson, G.A., 1991, High and moderate affinity pathways for a-thrombin-induced platelet activation, Proc Soc Exp Biol Med,198:792.PubMedGoogle Scholar
  26. Gupta, S.K., Diez, E., Heasley, L.E., Osawa, S., and Johnson, G.L., 1990, AG protein mutant that inhibits thrombin and purinergic receptor activation of phospholipase A2, Science, 249:662.PubMedCrossRefGoogle Scholar
  27. Hallam, T.J., Daniel, J.L., Kendrick Jones, J., and Rink, T.J., 1985, Relationship between cytoplasmic free calcium and myosin light chain phosphorylation in intact platelets, Biochem J, 232:373.PubMedGoogle Scholar
  28. Harmon, J.T., and Jamieson, G.A., 1986, Activation of platelets by alpha-thrombin is a receptor-mediated event, J Biol Chem, 261:15928.PubMedGoogle Scholar
  29. Harmon, J.T., and Jamieson, G.A., 1988, Platelet activation by thrombin in the absence of the high affinity thrombin receptor, Biochemistry,27:2151.PubMedCrossRefGoogle Scholar
  30. Haslam, R.J., Lynham, J.A., and Fox, J.E.B., 1979, Effects of collagen, ionophore A23187 and prostaglandin El on the phosphorylation of specific proteins in blood platelets, Biochem J, 178:397.PubMedGoogle Scholar
  31. Hathway, D.R., and Adelstein, R.S., 1979, Human platelet myosin light chain kinase requires the calciumbinding protein calmodulin for activity, Proc Natl Acad Sci USA, 76:1653.CrossRefGoogle Scholar
  32. Hausdorff, W.P., Caron, M.G., and Lefkowitz, R.J., 1990, Turning off the signal: desensitization of betaadrenergic receptor function, FASEB J, 4:2881.PubMedGoogle Scholar
  33. Hirata, M., Hayashi, Y., Ushikubi, F., Nakanishi, S., and Narumiya, S., 1991, Cloning and expression of cDNA for a human thromboxane A2 receptor, Nature,349:617.PubMedCrossRefGoogle Scholar
  34. Honda, Z., Nakamura, M., Miki, I., Minami, M., Watanabe, T., Seyama, Y., Okado, H., Toh, H., Ito, K., Miyamoto, T., and Shimizu, T., 1991, Cloning by functional expression of platelet-activating factor receptor from guinea-pig lung, Nature, 349:342.PubMedCrossRefGoogle Scholar
  35. Huang, E.M., and Detwiler, T.C., 1987, Thrombin-induced phosphoinositide hydrolysis in platelets. Receptor occupancy and desensitization, Biochem J, 242:11.PubMedGoogle Scholar
  36. Huang, R., Sorisky, A., Church, W.R., Simons, E.R., and Rittenhouse, S.E., 1991, “Thrombin” receptor-directed ligand accounts for activation by thrombin of platelet phospholipase C and accumulation of 3-phosphorylated phosphoinositides, J Biol Chem, 266:18435.PubMedGoogle Scholar
  37. Hung, D.T., Thien-Khai, H.V., Nelken, N.A., and Coughlin, S.R., 1992, Thrombin-induced proteolytic events in non-platelet cells are mediated by the unique proteolytic mechanism established for the cloned platelet thrombin receptor, J Cell Biol,116:827.PubMedCrossRefGoogle Scholar
  38. Iiri, T., Tohkin, M., Morishima, N., Ohoka, Y., Ui, M., and Katada, T., 1989, Chemotactic peptide receptor-supported ADP-ribosylation of a pertussis toxin substrate GTP-binding protein by cholera toxin in neutrophil-type HL-60 cells, J Biol Chem, 264:21394.PubMedGoogle Scholar
  39. Jaffe, E.A., Grulich, J., Weksler, B.B., Hampel, G., and Watanabe, K., 1987, Correlation between thrombin-induced prostacyclin production and inositol trisphosphate and cytosolic free calcium levels in cultured human endothelial cells, J Biol Chem, 262:8557.PubMedGoogle Scholar
  40. Jamieson, G.A., and Okumura, T., 1978, Reduced thrombin binding and aggregation in Bernard-Soulier platelets, J Clin Invest, 61:861.PubMedCrossRefGoogle Scholar
  41. Jelsema, C.L., and Axelrod, J., 1987, Stimulation of phospholipase A2 activity in bovine rod outer segments by the beta gamma subunits of transducin and its inhibition by the alpha subunit, Proc Nall Acad Sci USA, 84:3623.CrossRefGoogle Scholar
  42. Jones, L.G., McDonough, P.M., and Brown, J.H., 1989, Thrombin and trypsin act at the same site to stimulate phosphoinositide hydrolysis and calcium mobilization, Mol Pharmacol, 36:142.PubMedGoogle Scholar
  43. Kajiyama, Y., Murayama, T., and Nomura, Y., 1989, Pertussis toxin-sensitive GTP-binding proteins may regulate phospholipase A2 in response to thrombin in rabbit platelets, Arch Biochem Biophys, 274:200.PubMedCrossRefGoogle Scholar
  44. Kaser-Glanzmann, R., Gerber, E., and Luscher, E.F., 1979, Regulation of the intracellular calcium level in human blood platelets: cAMP dependent phosphorylation of a 22,000 Dalton component in isolated Ca2+-accumulating vesicles, Biochim Biophys Acta, 558:34.Google Scholar
  45. Kelleher, D.J., Pessin, J.E., Ruoho, A.E., and Johnson, G.L., 1984, Phorbol ester induces desensitization of adenylate cyclase and phosphorylation of the β-drenergic receptor in turkey erythrocytes, Proc Natl Acad Sci USA, 81:4316.PubMedCrossRefGoogle Scholar
  46. Kemp, B.E., and Pearson, R.B., 1990, Protein kinase recognition sequence motifs, Trends in Biochemical Sciences, 15:342.PubMedCrossRefGoogle Scholar
  47. Kim, D., Lewis, D.L., Graziadei, L., Neer, E.J., Bar-Sagi, D., and Clapham, D.E., 1989, G-protein βgamma-subunits activate the cardiac muscarinic K+-channel via phospholipase A2, Nature, 337:557.PubMedCrossRefGoogle Scholar
  48. Kobilka, B.K., Matsui, H., Kobilka, T.S., Yang Feng, T.L., Francke, U., Caron, M.G., Lefkowitz, R.J., and Regan, J.W., 1987, Cloning, sequencing, and expression of the gene coding for the human platelet alpha 2-adrenergic receptor, Science, 238:650.PubMedCrossRefGoogle Scholar
  49. Kramer, R., Checani, G., Deykin, A., Pritzker, C., and Deykin, D., 1986, Solubilization and properties of Ca2+-dependent human platelet phospholipase A2, Biochim Biophys Acta, 878:394.PubMedCrossRefGoogle Scholar
  50. Laposata, M., Krueger, C.M., and Saffitz, J.E., 1987, Selective uptake of [3Н]arachidonic acid into the dense tubular system of human platelets, Blood, 70:832.PubMedGoogle Scholar
  51. Leeb-Lundberg, L.M.F., Cotecchia, S., Lomasney, J.W., DeBernardis, J.F., Lefkowitz, R.J., and Caron, M.G., 1985, Phorbol esters promote αl-adrenergic receptor phosphorylation and receptor uncoupling from inositol phospholipid metabolism, Proc Natl Acad Sci USA, 82:5651.PubMedCrossRefGoogle Scholar
  52. Lewis, J.M., Woolkalis, M.J., Gerton, G.L., Smith, R.M., Jarett, L., and Manning, D.R., 1991, Subcellular distribution of the α subunit(s) of Gi: visualization by immunofluorescent and immunogold labeling, Cell Regulation, 2:1097.PubMedGoogle Scholar
  53. Liu, L-W., Vu, T-K.H., Esmon, C.T., and Coughlin, S.R., 1991, The region of the thrombin receptor resembling hirudin binds to thrombin and alters enzyme specificity, J Biol Chem, 266:16977.PubMedGoogle Scholar
  54. Lounsbury, K.M., Brass, L.F., and Manning, D.R., 1990, Phosphorylation of Gzα in human platelets: proximity to the amino-terminus of the subunit, J Cell Biol, 111:334a.Google Scholar
  55. Lounsbury, K.M., Casey, P.J., Brass, L.F., and Manning, D.R., 1991, Phosphorylation of Gz, in human platelets: selectivity and site of modification, J Biol Chem, 266:22051.PubMedGoogle Scholar
  56. Manning, D.R., and Brass, L.F., 1991, The role of GTP-binding proteins in platelet activation, Thromb Haemost, 66:393.PubMedGoogle Scholar
  57. Matsui, Y., Kikuchi, A., Kawata, M., Kondo, J., Teranishi, Y., and Takai, Y., 1990, Molecular cloning of smg p21B and identification of smg p21 purified from bovine brain and human platelets as smg p21B, Biochem Biophys Res Commun, 166:1010.PubMedCrossRefGoogle Scholar
  58. Murayama, T., Kajiyama, Y., and Nomura, Y., 1990, Histamine-stimulated and GTP-binding proteins-mediated phospholipase A2 activation in rabbit platelets, J Biol Chem, 265:4290.PubMedGoogle Scholar
  59. Nakashima, S., Hattori, H., Shirato, L., Takenaka, A., and Nozawa, Y., 1987, Differential sensitivity of arachidonic acid release and 1,2-diacylglycerol formation to pertussis toxin, GDPβS and NaF in saponin-permeabilized human platelets; possible evidence for distinct GTP-binding proteins involving phospholipase C and A2 activation, Biochem Biophys Res Commun, 148:971.PubMedCrossRefGoogle Scholar
  60. Ngaiza, J.R., and Jaffe, E.A., 1991, A 14 amino acid peptide derived from the amino terminus of the cleaved thrombin receptor elevates intracellular calcium and stimulates prostacyclin production in human endothelial cells, Biochem Biophys Res Commun, 179:1656.PubMedCrossRefGoogle Scholar
  61. Onorato, J.J., Palczewski, K., Regan, J.W., Caron, M.G., Lefkowitz, R.J., and Benovic, J.L., 1991, Role of acidic amino acids in peptide substrates of the beta-adrenergic receptor kinase and rhodopsin kinase, Biochemistry, 30:5118.PubMedCrossRefGoogle Scholar
  62. Paris, S., Magnaldo, I., and Pouysségur, J., 1988, Homologous desensitization of thrombin-induced phosphoinositide breakdown in hamster lung fibroblasts, J Biol Chem, 263:11250.PubMedGoogle Scholar
  63. Pipili-Synetos, E., Gershengorn, M.C., and Jaffe, E.A., 1990, Expression of functional thrombin receptors in Xenopus oocytes injected with human endothelial cell mRNA, Biochem Biophys Res Commun, 171:913.PubMedCrossRefGoogle Scholar
  64. Rasmussen, U.B., Vouret-Craviari, V., Jallat, S., Schlesinger, Y., Pagès, G., Pavirani, A., Lecocq, J-P., Pouysségur, J., and Van Obberghen-Schilling, E., 1991, cDNA Cloning and expression of a hamster α-thrombin receptor coupled to Ca2+ mobilization, FEES Letters, 288:123.CrossRefGoogle Scholar
  65. Raymond, J.R., 1991, Protein kinase C induces phosphorylation and desensitization of the human 5-HTIA receptor, J Biol Chem, 266:14747.PubMedGoogle Scholar
  66. Ryu, S.H., Kim, U-H., Wahl, M.I., Brown, A.B., Carpenter, G., Huang, K-P., and Rhee, S.G., 1990, Feedback regulation of phospholipase C-β by protein kinase C, J Biol Chem, 265:17941.PubMedGoogle Scholar
  67. Salter, R.D., Howell, D.N., and Cresswell, P., 1985, Genes regulating HLA class I antigen expression in T-B lymphoblast hybrids, Immunogenetics, 21:235.PubMedCrossRefGoogle Scholar
  68. Seiler, S.M., Michel, I.M., and Fenton, J.W.II., 1992, Involvement of the “tethered-ligand” receptor in thrombin inhibition of adenylate cyclase, Biochem Biophys Res Comtnun, 182:1296.CrossRefGoogle Scholar
  69. Shenker, A., Goldsmith, P., Unson, C.G., and Spiegel, A.M., 1991, The G protein coupled to the thomboxane A2 receptor in human platelets is a member of the novel Gq family, J Biol Chem, 266:9309.PubMedGoogle Scholar
  70. Sibley, D.R., Benovic, J.L., Caron, M.G., and Lefkowitz, R.J., 1987, Regulation of transmembrane signaling by receptor phosphorylation, Cell, 48:913.PubMedCrossRefGoogle Scholar
  71. Silk, S.T., Clejan, S., and Witkom, K., 1989, Evidence of GTP-binding protein regulation of phospholipase A2 activity in isolated human platelet membranes, J Biol Chem, 264:21466.PubMedGoogle Scholar
  72. Simmoteit, R., Schulzki, H-D., Palm, D., Mollner, S., and Pfeuffer, T., 1991, Chemical and functional analysis of components of adenylyl cyclase from human platelets treated with phorbolesters, FEES Lett, 285:99.CrossRefGoogle Scholar
  73. Smith, S.K., and Limbird, L.E., 1982, Evidence that human platelet alpha-adrenergic receptors coupled to inhibition of adenylate cyclase are not associated with the subunit of adenylate cyclase ADP-ribosylated by cholera toxin, J Biol Chem, 257:10471.PubMedGoogle Scholar
  74. Smrcka, A.V., Hepler, J.R., Brown, K.O., and Sternweis, P.C., 1991, Regulation of polyphosphoinositide -specific phospholipase C activity by purified Gq, Science, 251:804.PubMedCrossRefGoogle Scholar
  75. Strathmann, M., and Simon, M.I., 1990, G protein diversity: a distinct class of a subunits is present in vertebrates and invertebrates, Proc Natl Acad Sci USA, 87:9113.PubMedCrossRefGoogle Scholar
  76. Strathmann, M.P., and Simon, M.I., 1991, Gα12 and Gα13 subunits define a fourth class of G protein a subunits, Proc Natl Acad Sci USA, 88:5582.PubMedCrossRefGoogle Scholar
  77. Tang, W-J., and Gilman, A.G., 1991, Type-specific regulation of adenylyl cyclase by G protein Bganuna subunits, Science, 254:1500.PubMedCrossRefGoogle Scholar
  78. Taylor, S.J., Chae, H.Z., Rhee, S.G., and Exton, J.H., 1991, Activation of the B1 isozyme of phospholipase C by a subunits of the Gq class of G proteins. Nature, 350:516.PubMedCrossRefGoogle Scholar
  79. Taylor, S.J., and Exton, J.H., 1991, Two a subunits of the Gq class of G proteins stimulate phosphoinositide phospholipase C-β1 activity, FEES Letts, 286:214.CrossRefGoogle Scholar
  80. Van Obberghen-Schilling, E., Chambard, J.C., Lory, P., Nargeot, J., and Pouysségur, J., 1990, Functional expression of Ca2+-mobilizing a-thrombin receptors in mRNA-injected Xenopus oocytes, FEES Letts, 262:330.CrossRefGoogle Scholar
  81. Vassallo, R.R. Jr., Hoxie, J.A., and Brass, L.F., 1992a, Antibodies to the N-terminus of the thrombin receptor inhibit platelet activation by thrombin, Clin Res, in press.Google Scholar
  82. Vassallo, R.R. Jr., Kieber-Emmons, T., Cichowski, K., and Brass, L.F., 1992b, Structure/function relationships in the activation of platelet thrombin receptors by receptor-derived peptides, J Biol Chem, 267:6081.Google Scholar
  83. Vouret-Craviari, V., Van Obberghen-Schilling, E., Rasmussen, U.B., Pavirani, A., Lecocq, J-P., and Pouysségur, J., 1992, Synthetic α-thrombin receptor peptides activate G protein-coupled signaling pathways but are unable to induce mitogenesis, Mol Biol Cell, 3:95.PubMedGoogle Scholar
  84. Vu, T-K.H., Hung, D.T., Wheaton, V.I., and Coughlin, S.R., 1991a, Molecular cloning of a functional thrombin receptor reveals a novel proteolytic mechanism of receptor activation, Cell, 64:1057.CrossRefGoogle Scholar
  85. Vu, T-K.H., Wheaton, V.I., Hung, D.T., Charo, I., and Coughlin, S.R., 1991b, Domains specifying thrombin-receptor interaction, Nature, 353:674.CrossRefGoogle Scholar
  86. Wallach, D., Davies, P.J.A., and Pastan, I., 1978, Cyclic AMP-dependent phosphorylation of filamin in mammalian smooth muscle, J Biol Chem, 253:4739.PubMedGoogle Scholar
  87. Wardell, M.R., Reynolds, C.C., Berndt, M.C., Wallace, R.W., and Fox, J.E.B., 1989, Platelet glycoprotein Ibβ is phosphorylated on serine 166 by cyclic AMP-dependent protein kinase, J Biol Chem, 264:15656.PubMedGoogle Scholar
  88. Weiss, E.R., Kelleher, D.J., Woof, C.W., Soparkar, S., Osawa, S., Heasley, L.E., and Johnson, G.L., 1988, Receptor activation of G proteins, FASEB J, 2:2841.PubMedGoogle Scholar
  89. White, T.E., Lacal, J-C., Reep, B., Fischer, T.H., Lapetina, E.G., and White, G.C. II., 1990, Thrombolamban, the 22-kDa platelet substrate of cyclic AMP-dependent protein kinase, is immunologically homologous with the Ras family of GTP-binding proteins, Proc Nail Acad Sci USA, 87:758.CrossRefGoogle Scholar
  90. Williams, A., Woolkalis, M.J., Poncz, M., Manning, D.R., Gewirtz, A., and Brass, L.F., 1990, Identification of the pertussis toxin-sensitive G proteins in platelets, megakaryocytes and HEL cells, Blood, 76:721.PubMedGoogle Scholar
  91. Yoshimoto, T., Yamamoto, S., Okuma, M., and Hayaishi, O., 1977, Solubilization and resolution of thromboxane synthesizing system from microsomes of bovine blood platelets, J Biol Chem, 252:5871.PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media New York 1993

Authors and Affiliations

  • Lawrence F. Brass
    • 1
  • James A. Hoxie
    • 1
  • Thomas Kieber-Emmons
    • 1
  • David R. Manning
    • 1
  • Mortimer Poncz
    • 1
  • Marilyn Woolkalis
    • 1
  1. 1.Departments of Medicine, PathologyPharmacology and Pediatrics of the University of Pennsylvania and the Wistar InstituteUSA

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