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Platelet Function pp 43–69Cite as

Platelet Adhesion

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Part of the book series: Contemporary Cardiology ((CONCARD))

Abstract

Platelet adhesion and ensuing thrombus formation play a central role in normal hemostasis as well as in the pathogenesis of acute coronary syndromes and thrombotic disorders. Circulating blood platelets adhere to sites of vascular injury through specific adhesion receptors despite the hemodynamic forces in flowing blood that oppose adhesion contacts. At high shear, this process is initiated by the reversible interaction between the platelet membrane glycoprotein (GP)Ib-IX-V complex and von Willebrand factor (vWF) bound to subendothelial components, following disruption of the endothelial cell lining of a blood vessel. Unique biomechanical properties of the GPIb-IX-V/vWF interaction permit the initial capture of platelets under high shear flow conditions (1,2). Once tethered to the vessel wall, platelets form irreversible adhesion bonds through the interaction of platelet receptors with specific subendothelial matrix proteins and plasma proteins immobilized at the site of injury. In addition to mediating platelet adhesion, platelet receptors trigger intracellular signaling events that lead to platelet activation and the conversion of surface integrin αIIbβ3 into a form that is competent to bind soluble adhesive ligands such as plasma vWF and fibrinogen, which facilitate the crosslinking (aggregation) and further activation of platelets, providing strength and stability to the growing thrombus. The formation of a platelet plug stabilized by an insoluble fibrin network serves to prevent further blood loss from a damaged vessel.

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References

  1. Savage B, Saldivar E, Ruggeri ZM. Initiation of platelet adhesion by arrest onto fibrinogen or translocation on von Willebrand factor. Cell 1996;84:289–297.

    PubMed  CAS  Google Scholar 

  2. Savage B, Almus-Jacobs F, Ruggeri ZM. Specific synergy of multiple substrate-receptor interactions in platelet thrombus formation under flow. Cell 1998;94:657–666.

    PubMed  CAS  Google Scholar 

  3. Kroll MH, Hellums JD, McIntire LV, Schafer AI, Moake JL. Platelets and shear stress. Blood 1996;88:1525–1541.

    PubMed  CAS  Google Scholar 

  4. Peterson DM, Stathopoulos NA, Giorgio TD, Hellums JD, Moake JL. Shear-induced platelet aggregation requires von Willebrand factor and platelet membrane glycoproteins Ib and IIb-IIIa. Blood 1987;69:625–628.

    PubMed  CAS  Google Scholar 

  5. Goto S, Ikeda Y, Saldivar E, Ruggeri ZM. Distinct mechanisms of platelet aggregation as a consequence of different shearing flow conditions. J Clin Invest 1998;101:479–486.

    PubMed  CAS  Google Scholar 

  6. Ruggeri ZM. Old concepts and new developments in the study of platelet aggregation. J Clin Invest 2000;105:699–701.

    PubMed  CAS  Google Scholar 

  7. Ruggeri ZM, Dent JA, Saldivar E. Contribution of distinct adhesive interactions to platelet aggregation in flowing blood. Blood 1999;94:172–178.

    PubMed  CAS  Google Scholar 

  8. Wu YP, Vink T, Schiphorst M, et al. Platelet thrombus formation on collagen at high shear rates is mediated by von Willebrand factor-glycoprotein Ib interaction and inhibited by von Willebrand factor-glycoprotein IIb/IIIa interaction. Arterioscler Thromb Vasc Biol 2000;20:1661–1667.

    PubMed  CAS  Google Scholar 

  9. Tsuji S, Sugimoto M, Miyata S, Kuwahara M, Kinoshita S, Yoshioka A. Real-time analysis of mural thrombus formation in various platelet aggregation disorders: distinct shear-dependent roles of platelet receptors and adhesive proteins under flow. Blood 1999;94:968–975.

    PubMed  CAS  Google Scholar 

  10. Romo GM, Dong JF, Schade AJ, et al. The glycoprotein Ib-IX-V complex is a platelet counterreceptor for P-selectin. J Exp Med 1999;190:803–814.

    PubMed  CAS  Google Scholar 

  11. Simon DI, Chen Z, Xu H, et al. Platelet glycoprotein Ibalpha is a counterreceptor for the leukocyte integrin Mac-1 (CD11b/CD18). J Exp Med 2000;192:193–204.

    PubMed  CAS  Google Scholar 

  12. Okumura T, Jamieson GA. Platelet glycocalicin: a single receptor for platelet aggregation induced by thrombin or ristocetin. Thromb Res 1976;8:701–706.

    PubMed  CAS  Google Scholar 

  13. Mazzucato M, De Marco L, Masotti A, Pradella P, Bahou WF, Ruggeri ZM. Characterization of the initial α-thrombin interaction with glycoprotein Ibα in relation to platelet activation. J Biol Chem 1998;273:1880–1887.

    PubMed  CAS  Google Scholar 

  14. Bradford HN, Dela Cadena RA, Kunapuli SP, Dong J-F, Lopez JA, Colman RW. Human kininogens regulate thrombin binding to platelets through the glycoprotein Ib-IX-V complex. Blood 1997;90:1508–1515.

    PubMed  CAS  Google Scholar 

  15. Baglia FA, Badellino KO, Li CQ, Lopez JA, Walsh PN. Factor XI binding to the platelet glycoprotein Ib-IX-V complex promotes factor XI activation by thrombin. J Biol Chem 2002;277:1662–1668.

    PubMed  CAS  Google Scholar 

  16. Bradford HN, Pixley RA, Colman RW. Human factor XII binding to the glycoprotein Ib-IX-V complex inhibits thrombin-induced platelet aggregation. J Biol Chem 2000;275:22756–22763.

    PubMed  CAS  Google Scholar 

  17. Jackson SP, Mistry N, Yuan Y. Platelets and the injured vessel wall—“rolling into action.” Focus on glycoprotein Ib/V/IX and the platelet cytoskeleton. Trends Cardiovasc Med 2000;10:192–197.

    PubMed  CAS  Google Scholar 

  18. Ware J. Molecular analyses of the platelet glycoprotein Ib-IX-V receptor. Thromb Haemost 1998;79:466–478.

    PubMed  CAS  Google Scholar 

  19. Mazzucato M, Pradella P, Cozzi MR, De Marco L, Ruggeri ZM. Sequential cytoplasmic calcium signals in a two-stage platelet activation process induced by the glycoprotein Ibα mechanoreceptor. Blood 2002;100:2793–2800.

    PubMed  CAS  Google Scholar 

  20. Yap CL, Anderson KE, Hughan SC, Dopheide SM, Salem HH, Jackson SP. Essential role for phosphoinositide 3-kinase in shear-dependent signaling between platelet glycoprotein Ib/V/IX and integrin αIIbβ3. Blood 2002;99:151–158.

    PubMed  CAS  Google Scholar 

  21. Andrews RK, Shen Y, Gardiner EE, Dong J, Lopez JA, Berndt MC. The glycoprotein Ib-IX-V complex in platelet adhesion and signaling. Thromb Haemost 1999;82:357–364.

    PubMed  CAS  Google Scholar 

  22. Berndt MC, Shen Y, Dopheide SM, Gardiner EE, Andrews RK. The vascular biology of the glycoprotein Ib-IX-V complex. Thromb Haemost 2001;86:178–188.

    PubMed  CAS  Google Scholar 

  23. Andrews RK, Berndt MC. Adhesion-dependent signalling and the initiation of haemostasis and thrombosis. Histol Histopathol 1998;13:837–844.

    PubMed  CAS  Google Scholar 

  24. Du X, Beutler L, Ruan C, Castaldi PA, Berndt MC. Glycoprotein Ib and glycoprotein IX are fully complexed in the intact platelet membrane. Blood 1987;69:1524–1527.

    PubMed  CAS  Google Scholar 

  25. Breit SN, Green I. Modulation of endothelial cell synthesis of von Willebrand factor by mononuclear cell products. Haemostasis 1988;18:137–145.

    PubMed  CAS  Google Scholar 

  26. Lopez JA. The platelet glycoprotein Ib-IX complex. Blood Coagul Fibrinolysis 1994;5:97–119.

    PubMed  CAS  Google Scholar 

  27. Berndt MC, Gregory C, Kabral A, Zola H, Fournier D, Castaldi PA. Purification and preliminary characterization of glycoprotein Ib complex in the human platelet membrane. Eur J Biochem 1985;151:637–649.

    PubMed  CAS  Google Scholar 

  28. Modderman PW, Admiraal LG, Sonnenberg A, Von dem Borne AE. Glycoproteins V and Ib-IX form a noncovalent complex in the platelet membrane. J. Biol Chem 1992;267:364–369.

    PubMed  CAS  Google Scholar 

  29. Kovacsovics TJ, Hartwig JH. Thrombin-induced GPIb-IX centralization on the platelet surface requires actin assembly and myosin II activation. Blood 1996;87:618–629.

    PubMed  CAS  Google Scholar 

  30. van Zanten GH, Heijnen HFG, Wu Y, et al. A fifty percent reduction of platelet surface glycoprotein Ib does not affect platelet adhesion under flow conditions. Blood 1998;91:2353–2359.

    PubMed  Google Scholar 

  31. Hourdille P, Heilmann E, Combrie R, Winckler J, Clemetson KJ, Nurden AT. Thrombin induces a rapid redistribution of glycoprotein Ib-IX complexes within the membrane systems of activated human platelets. Blood 1990;76:1503–1513.

    PubMed  CAS  Google Scholar 

  32. George JN, Torres MM. Thrombin decreases von Willebrand factor binding to platelet glycoprotein Ib. Blood 1988;71:1253–1259.

    PubMed  CAS  Google Scholar 

  33. Michelson AD, Barnard MR. Thrombin-induced changes in platelet membrane glycoproteins Ib, IX, and IIb-IIIa complex. Blood 1987;70:1673–1678.

    PubMed  CAS  Google Scholar 

  34. Michelson AD, Benoit SE, Furman MI, Barnard MR, Nurden P, Nurden AT. The platelet surface expression of glycoprotein V is regulated by two independent mechanisms: proteolysis and the reversible cytoskeletal-mediated redistrbution to the surface-connected canalicular system. Blood 1996;87:1396–1408.

    PubMed  CAS  Google Scholar 

  35. Handa M, Titani K, Holland LZ, Roberts JR, Ruggeri ZM. The von Willebrand factor-binding domain of platelet membrane glycoprotein Ib. Characterization by monoclonal antibodies and partial amino acid sequence analysis of proteolytic fragments. J Biol Chem 1986;261:12579–12585.

    PubMed  CAS  Google Scholar 

  36. Vicente V, Kostel PJ, Ruggeri ZM. Isolation and functional characterization of the von Willebrand factor-binding domain located between residues His1-Arg293 of the alpha-chain of glycoprotein Ib. J Biol Chem 1988;263:18473–18479.

    PubMed  CAS  Google Scholar 

  37. Vicente V, Houghten RA, Ruggeri ZM. Identification of a site in the alpha chain of platelet glycoprotein Ib that participates in von Willebrand factor binding. J Biol Chem 1990;265:274–280.

    PubMed  CAS  Google Scholar 

  38. Uff S, Clemetson JM, Harrison T, Clemetson KJ, Emsley J. Crystal structure of the platelet glycoprotein Ibalpha N-terminal domain reveals an unmasking mechanism for receptor activation. J Biol Chem 2002;277:35,657–35,663.

    PubMed  CAS  Google Scholar 

  39. Huizinga EG, Tsuji S, Romijn RAP, et al. Structures of glycoprotein Ibα and its complex with von Willebrand factor A1 domain. Science 2002;297:1176–1129.

    PubMed  CAS  Google Scholar 

  40. Dong J-F, Li CQ, Lopez JA. Tyrosine sulfation of the glycoprotein Ib-IX complex: identification of sulfated residues and effect on ligand binding. Biochemistry 1994;33:13946–13953.

    PubMed  CAS  Google Scholar 

  41. Marchese P, Murata M, Mazzucato M, et al. Identification of three tyrosine residues of glycoprotein Ibα with distinct roles in von Willebrand factor and α-thrombin binding. J Biol Chem 1995;270:9571–9578.

    PubMed  CAS  Google Scholar 

  42. Vasudevan S, Roberts JR, McClintock RA, et al. Modeling and functional analysis of the interaction between von Willebrand factor A1 domain and glycoprotein Iba. J Biol Chem 2000;275:12763–12768.

    PubMed  CAS  Google Scholar 

  43. Andrews RK, Fox JEB. Identification of a region in the cytoplasmic domain of the platelet membrane glycoprotein Ib-IX complex that binds to purified actin-binding protein. J Biol Chem 1992;267:18605–18611.

    PubMed  CAS  Google Scholar 

  44. Fox JE, Boyles JK, Berndt MC, Steffen PK, Anderson LK. Identification of a membrane skeleton in platelets. J Cell Biol 1988;106:1525–1538.

    PubMed  CAS  Google Scholar 

  45. Du X, Fox JE, Pei S. Identification of a binding sequence for the 14-3-3 protein within the cytoplasmic domain of the adhesion receptor, platelet glycoprotein Iba. J Biol Chem 1996;271:7362–7367.

    PubMed  CAS  Google Scholar 

  46. Bodnar RJ, Gu M, Li Z, Englund GD, Du X. The cytoplasmic domain of the platelet glycoprotein Ibα is phosphorylated at serine 609. J Biol Chem 1999;274:33474–33479.

    PubMed  CAS  Google Scholar 

  47. Munday AD, Berndt MC, Mitchell CA. Phosphoinositide 3-kinase forms a complex with platelet membrane glycoprotein Ib-IX-V complex and 14-3-3zeta. Blood 2000;96:577–584.

    PubMed  CAS  Google Scholar 

  48. Calverley DC, Kavanaugh J, Rogh GJ. Human signaling protein 14-3-3ζ interacts with platelet glycoprotein Ib subunits Ibα and Ibβ. Blood 1998;91:1295–1303.

    PubMed  CAS  Google Scholar 

  49. Andrews RK, Harris SJ, McNally T, Berndt MC. Binding of purified 14-3-3 ζ signaling protein to discrete amino acid sequences within the cytoplasmic domain of the platelet membrane glycoprotein Ib-IX-V complex. Biochemistry 1998;37:638–647.

    PubMed  CAS  Google Scholar 

  50. Feng S, Christodoulides N, Resendiz JC, Berndt MC, Kroll MH. Cytoplasmic domains of GpIbalpha and GpIbbeta regulate 14-3-3zeta binding to GpIb/IX/V. Blood 2000;95:551–557.

    PubMed  CAS  Google Scholar 

  51. Andrews RK, Munday AD, Mitchell CA, Berndt MC. Interaction of calmodulin with cytoplasmic domain of the platelet membrane glycoprotein Ib-IX-V complex. Blood 2001;98:681–687.

    PubMed  CAS  Google Scholar 

  52. Kroll MH, Harris TS, Moake JL, Handin RI, Schafer AI. von Willebrand Factor binding to platelet GPIb initiates signals for platelet activation. J Clin Invest 1991;88:1568–1573.

    PubMed  CAS  Google Scholar 

  53. Ramakrishnan V, DeGuzman F, Bao M, Hall SW, Leung LL, Phillips DR. A thrombin receptor function for platelet glycoprotein Ib-IX unmasked by cleavage of glycoprotein V. Proc Natl Acad Sci USA 2001;98:1823–1828.

    PubMed  CAS  Google Scholar 

  54. Kasirer-Friede A, Ware J, Leng L, Marchese P, Ruggeri ZM, Shattil SJ. Lateral clustering of platelet GP Ib-IX complexes leads to up-regulation of the adhesive function of integrin αIIbβ3. J Biol Chem 2002;277:11949–11956.

    PubMed  CAS  Google Scholar 

  55. Satoh K, Asazuma N, Yatomi Y, et al. Activation of protein-tyrosine kinase pathways in human platelets stimulated with the A1 domain of von Willebrand factor. Platelets 2000;11:171–176.

    PubMed  CAS  Google Scholar 

  56. Falati S, Edmead CE, Poole AW. Glycoprotein Ib-V-IX, a receptor for von Willebrand factor, couples physically and functionally to the Fc receptor gammachain, Fyn, and Lyn to activate human platelets. Blood 1999;94:1648–1656.

    PubMed  CAS  Google Scholar 

  57. Torti M, Bertoni A, Canobbio I, Sinigaglia F, Lapetina EG, Balduini C. Rap 1B and Rap2B translocation to the cytoskeleton by von Willebrand factor involves FcgammaII receptor-mediated protein tyrosine physphorylation. J Biol Chem 1999;274:13690–13697.

    PubMed  CAS  Google Scholar 

  58. Sullam PM, Hyun WC, Szollosi J, Dong J, Foss WM, López JA. Physical proximity and functional interplay of the glycoprotein Ib-IX-V complex and the Fc receptor FcgammaRIIA on the platelet plasma membrane. J Biol Chem 1998;273:5331–5336.

    PubMed  CAS  Google Scholar 

  59. Watson SP, Asazuma N, Atkinson B, et al. The role of ITAM-and ITIM-coupled receptors in platelet activation by collagen. Thromb Haemost 2001;86:276–288.

    PubMed  CAS  Google Scholar 

  60. Cunningham JG, Meyer SC, Fox JEB. The cytoplasmic domain of the α-subunit of glycoprotein (GP) Ib mediates attachment of the entire GP Ib-IX complex to the cytoskeleton and regulates von Willebrand factor-induced changes in cell morphology. J Biol Chem 1996;271:11581–11587.

    PubMed  CAS  Google Scholar 

  61. Du X, Harris SJ, Tetaz TJ, Ginsberg MH, Berndt MC. Association of a phospholipase A2 (14-3-3 protein) with the platelet glycoprotein Ib-IX complex. J Biol Chem 1994;269:18287–18290.

    PubMed  CAS  Google Scholar 

  62. Gu M, Xi X, Englund GD, Berndt MC, Du X. Analysis of the roles of 14-3-3 in the platelet glycoprotein Ib-IX-mediated activation of integrin alpha (IIB)beta(3) using a reconstituted mammalian cell expression model. J Cell Biol 1999;147:1085–1096.

    PubMed  CAS  Google Scholar 

  63. Santoro SA. Identification of a 160,000 dalton platelet membrane protein that mediates the initial divalent cation-dependent adhesion of platelets to collagen. Cell 1986;46:913–920.

    PubMed  CAS  Google Scholar 

  64. Kunicki TJ, Nugent DJ, Staats SJ, Orchekowski RP, Wayner EA, Carter WG. The human fibroblast class II extracellular matrix receptor mediates platelet adhesion to collagen and is identical to the platelet glycoprotein Ia-IIa complex. J Biol Chem 1988;263:4516–4519.

    PubMed  CAS  Google Scholar 

  65. Nieuwenhuis HK, Akkerman JWN, Houdijk WPM, Sixma JJ. Human blood platelets showing no response to collagen fail to express surface glycoprotein Ia. Nature 1985;318:470–472.

    PubMed  CAS  Google Scholar 

  66. Moroi M, Jung SM, Okuma M, Shinmyozu K. A patient with platelets deficient in glycoprotein VI that lack both collagen-induced aggregation and adhesion. J Clin Invest 1989;84:1440–1445.

    PubMed  CAS  Google Scholar 

  67. Moroi M, Jung SM, Shinmyozu K, Tomiyama Y, Ordinas A, Diaz-Ricart M. Analysis of platelet adhesion to a collagen-coated surface under flow conditions: involvement of glycoprotein VI in the platelet adhesion. Blood 1996;88:2081–2092.

    PubMed  CAS  Google Scholar 

  68. Clemetson JM, Polgar J, Magnenat E, Wells TN, Clemetson KJ. The platelet collagen receptor glycoprotein VI is a member of the immunoglobulin superfamily closely related to FcαR and the natural killer receptors. J Biol Chem 1999;274:29019–29024.

    PubMed  CAS  Google Scholar 

  69. Clemetson KJ, Clemetson JM. Platelet collagen receptors. Thromb Haemost 2001;86:189–197.

    PubMed  CAS  Google Scholar 

  70. Arai M, Yamamoto N, Moroi M, Akamatsu N, Fukutake K, Tanoue K. Platelets with 10% of the normal amount of glycoprotein VI have an impaired response to collagen that results in a mild bleeding tendency. Br J Haematol 1995; 89:124–130.

    PubMed  CAS  Google Scholar 

  71. Kehrel B, Balleisen L, Kokott R, et al. Deficiency of intact thrombospondin and membrane glycoprotein Ia in platelets with defective collagen-induced aggregation and spontaneous loss of disorder. Blood 1988;71:1074–1078.

    PubMed  CAS  Google Scholar 

  72. Chiang TM, Rinaldy A, Kang AH. Cloning, characterization, and functional studies of a nonintegrin platelet receptor for type I collagen. J Clin Invest 1997;100:514–529.

    PubMed  CAS  Google Scholar 

  73. Asch AS, Liu I, Briccetti FM, et al. Analysis of CD36 binding domains: ligand specificity controlled by dephosphorylation of an ectodomain. Science 1993;262:1436–1440.

    PubMed  CAS  Google Scholar 

  74. Tandon NN, Kralisz U, Jamieson GA. Identification of glycoprotein IV (CD36) as a primary receptor for platelet-collagen adhesion. J Biol Chem 1989;264:7576–7583.

    PubMed  CAS  Google Scholar 

  75. Diaz-Ricart M, Tandon NN, Carretero M, Ordinas A, Bastida E, Jamieson GA. Platelets lacking functional CD36 (glycoprotein IV) show reduced adhesion to collagen in flowing whole blood. Blood 1993;82:491–496.

    PubMed  CAS  Google Scholar 

  76. Kehrel B, Kronenberg A, Rauterberg J, et al. Platelets deficient in glycoprotein IIIb aggregate normally to collagens type I and III but not to collagen type V. Blood 1993;82:3364–3370.

    PubMed  CAS  Google Scholar 

  77. Daniel JL, Dangelnaier C, Strouse R, Smith JB. Collagen induces normal signal transduction in platelets deficient in CD36 (platelet glycoprotein IV). Thromb Haemost 1994;72:353–356.

    Google Scholar 

  78. Sylvie M, Mangin P, Lenain N, et al. Platelet glycoprotein V binds to collagen and participates in platelet adhesion and aggregation. Blood 2001;98:1038–1046.

    Google Scholar 

  79. Phillips DR, Poh-Agin P. Platelet plasma membrane glycoproteins. Identification of a proteolytic substrate for thrombin. Biochem Biophys Res Commun 1977;75:940–947.

    PubMed  CAS  Google Scholar 

  80. Ramakrishnan V, Reeves PS, DeGuzman F, et al. Increased thrombin responsiveness in platelets from mice lacking glycoprotein V. Proc Natl Acad Sci USA 1999;96:13336–13341.

    PubMed  CAS  Google Scholar 

  81. Kahn ML, Diacovo TG, Bainton DF, Lanza F, Trejo J, Coughlin SR. Glycoprotein V-deficient platelets have undiminished thrombin responsiveness and do not exhibit a Bernard-Soulier phenotype. Blood 1999;94:4112–4121.

    PubMed  CAS  Google Scholar 

  82. Staatz WD, Rajpara SM, Wayner EA, William GC, Santoro SA. The membrane glycoprotein Ia-IIa (VLA-2) complex mediates the Mg++-dependent adhesion of platelets to collagen. J Cell Biol 1989;108:1917–1924.

    PubMed  CAS  Google Scholar 

  83. Pischel KD, Bluestein HG, Woods VL. Platelet glycoprotein Ia,Ic, and IIa are physicochemically indistinguishable from the very late activation antigens adhesion-related proteins of lymphocytes and other cell types. J Clin Invest 1988;81:505–513.

    PubMed  CAS  Google Scholar 

  84. Kunicki TJ. The role of platelet collagen receptor (glycoprotein Ia/IIa; integrin α2β1) polymorphisms in thrombotic disease. Curr Opin Haematol 2001;8:227–281.

    Google Scholar 

  85. Moshfegh K, Wuillemin WA, Redondo M. Association of two silent polymorphisms of platelet glycoprotein Ia/IIa receptor with risk of myocardial infarction: a case-control study. Lancet 1999;353:351–354.

    PubMed  CAS  Google Scholar 

  86. Santoso S, Kunicki TJ, Kroll H, Haberbosch W, Gardemann A. Association of the platelet glyroprotein Ia C807T gene polymophism with nonfatal myocardial infarction in younger patients. Blood 1999;93:2449–2453.

    PubMed  CAS  Google Scholar 

  87. Kunicki TJ, Kritzik M, Annis DS, Nugent DJ. Hereditary variation in platelet integrin α2β1 density is associated with two silent polymorphisms in the α2 gene coding sequence. Blood 1997;89:1939–1943.

    PubMed  CAS  Google Scholar 

  88. Kritzik M, Savage B, Nugent DJ, Santoso S, Ruggeri ZM, Kunicki TJ. Nucleotide polymorphisms in the α2 gene define multiple alleles which are associated with differences in platelet α2β1 density. Blood 1998;92:2382–2388.

    PubMed  CAS  Google Scholar 

  89. Takada Y, Hemler ME. The primary structure of the VLA-2/collagen receptor a2 subunit (platelet GPIa): Homology to other integrins and the presence of a possible collagen-binding domain. J Cell Biol 1989;109:397–407.

    PubMed  CAS  Google Scholar 

  90. Emsley J, King SL, Bergelson JM, Liddington RC. Crystal structure of the I domain from integrin α2β1. J Biol Chem 1997;272:28512–28517.

    PubMed  CAS  Google Scholar 

  91. Emsley J, Cruz M, Handin R, Liddington R. Crystal structure of the von Willebrand factor A1 domain and implications for the binding of platelet glycoprotein Ib. J Biol Chem 1998;273:10396–10401.

    PubMed  CAS  Google Scholar 

  92. Emsley J, Knight CG, Farndale RW, Barnes MJ, Liddington RC. Structural basis of collagen recognition by integrin α2β1. Cell 2000;100:47–51.

    Google Scholar 

  93. Knight CG, Morton LF, Onley DJ, et al. Identification in collagen type I of an integrin α2β1-binding site containing an essential GER sequence. J Biol Chem 1998;273:33287–33294.

    PubMed  CAS  Google Scholar 

  94. Dickeson SK, Walsh JJ, Santoro SA. Contributions of the I and EF hand domains to the divalent cation-dependent collagen binding activity of the α2β1 integrin. J Biol Chem 1997;272:7661–7668.

    PubMed  CAS  Google Scholar 

  95. Coller BS, Beer JH, Scudder LE, Steinberg MH. Collagen-platelet interactions: evidence for a direct interaction of collagen with platelet GPIa/IIa and an indirect interaction with platelet GPIIb/IIIa mediated by adhesive proteins. Blood 1989;74:182–192.

    PubMed  CAS  Google Scholar 

  96. Keely PJ, Parise LV. The α2β1 integrin is a necessary co-receptor for collagen-induced activation of syk and subsequent phosphorylation of phospholipase Cy2 in platelets. J Biol Chem 1996;271:26668–26676.

    PubMed  CAS  Google Scholar 

  97. Savage B, Ginsberg MH, Ruggeri ZM. Influence of fibrillar collagen structure on the mechanisms of platelet thrombus formation under flow. Blood 1999;94:2704–2715.

    PubMed  CAS  Google Scholar 

  98. Verkleij MW, Morton LF, Knight CG, de Groot PG, Barnes MJ, Sixma JJ. Simple collagen-like peptides support platelet adhesion under static but not under flow conditions: interaction via α2β1 von Willebrand factor with specific sequences in native collagen is a requirement to resist shear forces. Blood 1998;91:3808–3816.

    PubMed  CAS  Google Scholar 

  99. Wang R, Kini RM, Chung MC. Rhodocetin, a novel platelet aggregation inhibitor from the venom of Calloselasma rhodostoma (Malayan pit viper): synergistic and noncovalent interaction between its subunits. Biochemistry 1999;38:7584–7593.

    PubMed  CAS  Google Scholar 

  100. Marcinkiewicz C, Lobb RR, Marcinkiewicz MM, et al. Isolation and characterization of EMS16, a C-lectin type protein from Echis multisquamatus venom, a potent and selective inhibitor of the α2β1 integrin. Biochemistry 2000;39:9859–9867.

    PubMed  CAS  Google Scholar 

  101. Santoro SA, Walsh JJ, Staatz WD, Baranski KJ. Distinct determinants on collagen support α2β1 integrin mediated platelet adhesion and platelet activation. Cell Regul 1991;2:905–913.

    PubMed  CAS  Google Scholar 

  102. Morton LF, Peachey AR, Barnes MJ. Platelet-reactive sites in collagens type I and type III. Evidence for separate adhesion and aggregatory sites. Biochem J 1989;258:157–163.

    PubMed  CAS  Google Scholar 

  103. Ichinohe T, Takayama H, Ezumi Y, et al. Collagen-stimulated activation of Syk but not c-Src is severely compromised in human platelets lacking membrane glycoprotein VI. J Biol Chem 1997;272:63–68.

    PubMed  CAS  Google Scholar 

  104. Ichinohe T, Takayama H, Ezumi Y, Yanagi S, Yamamura H, Okuma M. Cyclic AMP-insensitive action of c-Src and Syk protein-tyrosine kinases through platelet membrane of glycoprotein VI. J Biol Chem 1995;270:28029–28036.

    PubMed  CAS  Google Scholar 

  105. Kehrel B, Wierwille S, Clemetson KJ, et al. Glycoprotein VI is a major collagen receptor for platelet activation: it recognizes the platelet-activating quaternary structure of collagen, whereas CD36, glycoprotein IIB/IIIa, and von Willebrand factor do not. Blood 1998;91:491–499.

    PubMed  CAS  Google Scholar 

  106. Kamiguti AS, Hay CR, Zuzel M. Inhibition of collagen-induced platelet aggregation as the result of cleavage of α2β1-integrin by the snake venom metalloproteinase jararhagin. Biochem J 1996;320:635–641.

    PubMed  CAS  Google Scholar 

  107. Kamiguti AS, Theakson RD, Watson SP, Bon C, Laing GD, Zuzel M. Distinct contributions of glycoprotein VI and α2β1 integrin to the induction of platelet protein tyrosine phosphorylation and aggregation. Arch Biochem Biophys 2000;374:356–362.

    PubMed  CAS  Google Scholar 

  108. Polanowska-Grabowska R, Geanacopoulos M, Gear ARL. Platelet adhesion to collagen via the α2β1 integrin under flow conditions causes rapid tyrosine phosphorylation of pp125FAK. Biochem J 1993;296:543–547.

    PubMed  CAS  Google Scholar 

  109. Zhou Q, Danglemaier C, Smith JB. The hemorrhagin catrocollastin inhibits collagen-induced platelet aggregation by binding to collagen via its disintegrin-like domain. Biochem Biophys Res Commun 1996;219:720–726.

    PubMed  CAS  Google Scholar 

  110. Huang T-F, Liu C-Z, Yang S-H. Aggretin, a novel platelet-aggregation inducer from snake Calloselasma rhodostoma venom, activates phospholipase C by acting as a glycoprotein Ia/IIa agonist. Biochem J 1995;309:1021–1027.

    PubMed  CAS  Google Scholar 

  111. Teng CM, Ko FN, Tsai IH, Hung ML, Huang TF. Trimucytin: a collagen-like aggregating inducer isolated from Trimeresurus mucrosquamatus snake venom. Thromb Haemost 1993;69:286–292.

    PubMed  CAS  Google Scholar 

  112. Inoue K, Ozaki Y, Satoh K, et al. Signal transduction pathways mediated by glycoprotein Ia/IIa in human platelets: comparison with those of glycoprotein VI. Biochem Biophys Res Commun 1999;246:114–120.

    Google Scholar 

  113. Chung CH, Au LC, Huang TF. Molecular cloning and sequence analysis of aggretin, a collagen-like platelet aggregation inducer. Biochem Biophys Res Commun 1999;263:723–727.

    PubMed  CAS  Google Scholar 

  114. Shin Y, Morita T. Rhodocytin, a functional novel platelet agonist belonging to the htreodimeric C-type lectin family, induces platelet aggregation independently of glycoprotein Ib. Biochem Biophys Res Commun 1998;245:741–745.

    PubMed  CAS  Google Scholar 

  115. Nakamura T, Kambayashi J, Okuma M, Tandon NN. Activation of the GP IIb-IIIa complex induced by platelet adhesion to collagen is mediated by both α2β1 integrin and GP VI. J Biol Chem 1999;274:11897–11903.

    PubMed  CAS  Google Scholar 

  116. Jung SM, Moroi M. Platelets interact with soluble and insoluble collagens through characteristically different reactions. J Biol Chem 1998;273:14827–14837.

    PubMed  CAS  Google Scholar 

  117. Sugiyama T, Okuma M, Ushikubi F, Sensaki S, Kanaji K, Uchino H. A novel platelet aggregating factor found in a patient with defective collagen-induced platelet aggregation and autoimmune thrombocytopenia. Blood 1987;69:1712–1720.

    PubMed  CAS  Google Scholar 

  118. Moroi M, Okuma M, Jung SM. Platelet adhesion to collagen-coated wells: analysis of this complex process and a comparison with the adhesion to matrigel-coated wells. Biochim Biophys Acta Mol Cell Res 1992;1137:1–9.

    CAS  Google Scholar 

  119. Jandrot-Perrus M, Busfield S, Lagrue A-H, et al. Cloning, characterization, and functional studies of human and mouse glycoprotein VI: a platelet-specific collagen receptor from the immunoglobulin superfamily. Blood 2000;96:1798–1807.

    PubMed  CAS  Google Scholar 

  120. Gibbins JM, Okuma M, Farndale R, Barnes M, Watson SP. Glycoprotein VI is the collagen receptor in platelets which underlies tyrosine phosphorylation of the Fc receptor gamma-chain. FEBS Lett 1997;413:255–259.

    PubMed  CAS  Google Scholar 

  121. Tsuji M, Ezumi Y, Arai M, Takayama H. A novel association of Fc receptor γ-chain with glycoprotein VI and their co-expression as a collagen receptor in human platelets. J Biol Chem 1997;272:23528–23531.

    PubMed  CAS  Google Scholar 

  122. Nieswandt B, Schulte V, Bergmeiser W, et al. Expression and function of the mouse collagen receptor glycoprotein VI is strictly dependent on its association with the FcRgamma chain. J Biol Chem 2000;275:23998–24002.

    PubMed  CAS  Google Scholar 

  123. Gibbins JM, Asselin J, Farndale R, Barnes M, Law CL, Watson SP. Tyrosine physphorylation of the Rc receptor γ-chain in collagen-stimulated platelets. J Biol Chem 1996;271:18095–18099.

    PubMed  CAS  Google Scholar 

  124. Poole A, Gibbins JM, Turner M, et al. The Fc receptor gamma-chain and the tyrosine kinase Syk are essential for activation of mouse platelets by collagen. EMBO J 1997;16:2333–2341.

    PubMed  CAS  Google Scholar 

  125. Gross BS, Lee JR, Clements JL, et al. Tyrosine phosphorylation of SLP-76 is downstream of Syk following stimulation of the collagen receptor in platelets. J Biol Chem 1999;274:5963–5971.

    PubMed  CAS  Google Scholar 

  126. Clements JL, Lee JR, Gross B, et al. Fetal hemorrhage and platelet dysfunction in SLP-76-deficient mice. J Clin Invest 1999;103:19–25.

    PubMed  CAS  Google Scholar 

  127. Berridge MJ. Inositol trisphostphate and calcium signalling. Nature 1993;361:315–325.

    PubMed  CAS  Google Scholar 

  128. Shattil SJ, Brass LF. Induction of the fibrinogen receptor on human platelets by intracellular mediators. J Biol Chem 1987;262:992–1000.

    PubMed  CAS  Google Scholar 

  129. Falet H, Barkalow KL, Pivniouk VI, Barnes MJ, Geha RS, Hartwig JH. Roles of SLP-76 phosphoinositide 3-kinase, and gelsolin in the platelet shape change initiated by the collagen receptor GPVI/FcRγ-chain complex. Blood 2000;96:3786–3792.

    PubMed  CAS  Google Scholar 

  130. Quek LS, Pasquet JM, Hers I, et al. Fyn and Lyn phosphorylate the Fc receptor γchain downstream of glycoprotein VI in murine platelets, and Lyn regulates a novel feedback pathway. Blood 2000;96:4246–4253.

    PubMed  CAS  Google Scholar 

  131. Judd BA, Koretzky GA. The role of the adaptor molecule SLP-76 in platelet function. Oncogene 2001;20:6291–6299.

    PubMed  CAS  Google Scholar 

  132. Pasquet J-M, Bobe R, Gross B, et al. A collagen related peptide regulates phospholipase Cγ2 via phosphatidylinositol 3-kinase in human platelets. Biochemistry 1999;342:171–177.

    CAS  Google Scholar 

  133. Gibbins JM, Briddon S, Shutes A, et al. The p85 subunit of phosphatidylinositol 3-kinase associates with the Fc receptor γ-chain and linker for activator T cells (LAT) in platelets stimulated by collagen and convulxin. J Biol Chem 1998;273:34437–34443.

    PubMed  CAS  Google Scholar 

  134. Lagrue AH, Francischetti IM, Guimarães JA, Jandrot-Perrus M. Phosphatidylinositol 3′-kinase and tyrosine-phosphatase activation positively modulates convulxin-induced platelet activation: comparison with collagen. FEBS Lett 1999;448:95–100.

    PubMed  CAS  Google Scholar 

  135. Massberg S, Gawaz M, Gruner S, et al. A crucial role of glycoprotein VI for platelet recruitment to the injured arterial wall in vivo. J Exp Med 2003;197:41–49.

    PubMed  CAS  Google Scholar 

  136. Kato K, Kanaji T, Russell S, et al. The contribution of glycoprotein VI to stable platelet adhesion and thrombus formation illustrated by targeted gene deletion. Blood 2003;102:1701–1707.

    PubMed  CAS  Google Scholar 

  137. Nieswandt B, Schulte V, Bergmeier W, et al. Long-term antithrombotic protection by in vivo depletion of platelet glycoprotein VI in mice. J Exp Med 2001;193:459–470.

    PubMed  CAS  Google Scholar 

  138. Dohlman HG, Thorner J, Caron MG, Kefkowitz RJ. Model systems for the study of seven-transmembrane-segment receptors. Annu Rev Biochem 1991;60:653–688.

    PubMed  CAS  Google Scholar 

  139. Hirata M, Hayashi Y, Ushikubi F, et al. Cloning and expression of cDNA for a human thromboxane A2 receptor. Nature 1991;349:617–620.

    PubMed  CAS  Google Scholar 

  140. Katsuyama M, Sugimoto Y, Namba T, et al. Cloning and expression of a cDNA for the human prostaglandin receptor. FEBS Lett 1994;344:74–78.

    PubMed  CAS  Google Scholar 

  141. Burgers JA, Akkerman JW. Regulation of the receptor for platelet-activating factor on human platelets. Biochem J 1993;291:157–161.

    PubMed  CAS  Google Scholar 

  142. Bandoh K, Aoki J, Hosono H, et al. Molecular cloning and characterization of a novel human G-protein-coupled receptor, EDG7, for lysophosophatidic acid. J Biol Chem 1999;274:27776–27785.

    PubMed  CAS  Google Scholar 

  143. Abi-Younes S, Sauty A, Mach F, Sukhova GK, Libby P, Luster AD. The stromal cell-derived factor-1 chemokine is a potent platelet agonist highly expressed in atherosclerotic plaques. Circ Res 2000;86:131–138.

    PubMed  CAS  Google Scholar 

  144. Clemetson KJ, Clemetson JM, Proudfoot AE, Power CA, Baggiolini M, Wells TN. Functional expression of CCR1, CCR3, CCR4, and CXCR4 chemokine receptors on human platelets. Blood 2000;96:50–57.

    Google Scholar 

  145. Kowalska MA, Ratajczak MZ, Majka M, J et al. Stromal cell-derived factor 1 and macrophage-derived chemokine: 2 chemokines that activate platelets. Blood 2000;96:50–57.

    PubMed  CAS  Google Scholar 

  146. Caron MG, Kobilka BK, Frielle T, Bolanowski MA, Benovic JL, Lefkowitz RJ. Cloning of the cNDA and genes for the hamster and human β2-adrenergic receptors. J Recept Res 2000;8:7–21.

    Google Scholar 

  147. Kagaya A, Mikuni M, Yamamoto H, Muraoka S, Yamawaki S, Takahashi K. Heterologous supersensitization between serotonin2 and a2-adenergic receptor-mediated intracellular calcium mobilization in human platelets. J Neural Transm 1992;88:25–36.

    CAS  Google Scholar 

  148. Daniel JL, Dangelmaier C, Jin J, Ashby B, Smith JB, Kunapuli SP. Molecular basis for ADP-induced platelet activation. I. Evidence for three distinct ADP receptors on human platelets. J Biol Chem 1998;273:2024–2029.

    PubMed  CAS  Google Scholar 

  149. Cattaneo M, Gachet C. ADP receptors and clinical bleeding disorders. Arterioscler Thromb Vasc Biol 1999;19:2281–2285.

    PubMed  CAS  Google Scholar 

  150. Jin J, Daniel JL, Kunapuli SP. Molecular basis for ADP-induced platelet activation. II. The P2Y1 receptor mediates ADP-induced intracellular calcium mobilization and shape change in platelets. J Biol Chem 1998;273:2030–2034.

    PubMed  CAS  Google Scholar 

  151. Hollopeter G, Jantzen H-M, Vincent D, et al. Identification of the platelet ADP receptor targeted by antithrombotic drugs. Nature 2001;409:202–206.

    PubMed  CAS  Google Scholar 

  152. Zhang FL, Luo L, Gustafson E, et al. ADP is the cognate ligand for the orphan G-protein coupled receptor SP1999. J Biol Chem 2001;276:8608–8615.

    PubMed  CAS  Google Scholar 

  153. Jin J, Kunapuli SP. Coactivation of two different G protein-coupled receptors is essential for ADP-induced platelet aggregation. Proc Natl Acad Sci USA 1998;95:8070–8074.

    PubMed  CAS  Google Scholar 

  154. Hechler B, Léon C, Vial C, et al. The P2Y1 receptor is necessary for adenosine 5′-diphosphate-induced platelet aggregation. Blood 1998;92:152–159.

    PubMed  CAS  Google Scholar 

  155. Savi P, Beauverger P, Labouret C, et al. Role of P2Y1 purinoceptor in ADP-induced platelet activation. FEBS Lett 1998;422:291–295.

    PubMed  CAS  Google Scholar 

  156. Bauer M, Retzer M, Wilde JI, et al. Dichotomous regulation of myosin phosphorylation and shape change by Rho-kinase and calcium in intact human platelets. Blood 1999;94:1665–1672.

    PubMed  CAS  Google Scholar 

  157. Wilde JI, Retzer M, Seiss W, Watson SP. ADP-induced platelet shape change: an investigation of the signalling pathways involved and their dependence on the method of platelet preparation. Platelets 2000;11:286–295.

    PubMed  CAS  Google Scholar 

  158. Fabre J-E, Nguyen M, Latour A, et al. Decreased platelet aggregation, increased bleeding time and resistance to thromboembolism in P2Y1-deficient mice. Nat Med 1999;5:1199–1202.

    PubMed  CAS  Google Scholar 

  159. Léon C, Vial C, Gachet C, et al. The P2Y1 receptor is normal in a patient presenting a severe deficiency of ADP-induced platelet aggregation. Further evidence for a distinct P2 receptor responsible for adenylyl cyclase inhibition. Thromb Haemost 1999;81:775–781.

    PubMed  Google Scholar 

  160. Offermanns S, Toombs CF, Hu Y-H, Simon MI. Defective platelet activation in Gαq-deficient mice. Nature 1997;389:183–186.

    PubMed  CAS  Google Scholar 

  161. Gachet C. ADP receptors of platelets and their inhibitors. Thromb Haemost 2001;86:222–232.

    PubMed  CAS  Google Scholar 

  162. Cattaneo M, Lecchi A, Randi AM, McGregor JL, Mannucci PM. Identification of a new congenital defect of platelet function characterized by severe impairment of platelet responses to adenosine diphosphate. Blood 1992;80:2787–2796.

    PubMed  CAS  Google Scholar 

  163. Cattaneo M, Lecchi A, Lombardi R, Gachet C, Zighetti ML. Platelets from a patient heterozygous for the defect of P2CYC receptors have a secretion defect despite normal thromboxane A2 production and normal granule stores. Arterioscler Thromb Vasc Biol 2000;20:e101–e106.

    PubMed  CAS  Google Scholar 

  164. Nurden P, Savi P, Heilmann E, et al. An inherited bleeding disorder linked to a defective interaction between ADP and its receptor on platelets. J Clin Invest 1995;95:1612–1622.

    PubMed  CAS  Google Scholar 

  165. Léon C, Hechler B, Freund M, et al. Defective platelet aggregation and increased resistance to thrombosis in purinergic P2Y1 receptor-null mice. J Clin Invest 1999;104:1731–1737.

    PubMed  Google Scholar 

  166. Savi P, Herbert JM. Pharmacology of ticlopidine and clopidogrel. Haematologica 2000;85:73–77.

    Google Scholar 

  167. Ingall AH, Dixon J, Bailey A, et al. Antagonists of the platelet P2T receptor: a novel approach to anti-thrombotic therapy. J Med Chem 1999;42:213–220.

    PubMed  CAS  Google Scholar 

  168. Humphries RG. Pharmacology of AR-C69931MX and related compounds: from pharmacological tools to clinical trials. Haematologica 2000;85:66–72.

    Google Scholar 

  169. Savi P, Labouret C, Delesque N, Guette F, Lupker J, Herbert JM. P2y(12), a new platelet ADP receptor, target of clopidogrel. Biochem Biophys Res Commun 2001;283:379–383.

    PubMed  CAS  Google Scholar 

  170. Daniel NG, Goulet J, Bergeron M, Paquin R, Landry P-E. Antiplatelet drugs: is there a surgical risk? J Can Dental Assoc 2002;68:683–687.

    Google Scholar 

  171. Sharis PJ, Cannon CP, Loscalzo J. The antiplatelet effects of ticlopidine and clopidogrel. Ann Intern Med 1998;129:394–405.

    PubMed  CAS  Google Scholar 

  172. Vu T-KH, Hung DT, Wheaton VI, Coughlin SR. Molecular cloning of a functional thrombin receptor reveals a novel proteolytic mechanism of receptor activation. Cell 1991;64:1057–1068.

    PubMed  CAS  Google Scholar 

  173. Vu T-KH, Wheaton VI, Hung DT, Coughlin SR. Domains specifying thrombin-receptor interaction. Nature 1991;353:674–677.

    PubMed  CAS  Google Scholar 

  174. Chen J, Ishii M, Wang L, Ishii K, Coughlin SR. Thrombin receptor activation: confirmation of the intramolecular tethered liganding hypothesis and discovery of an alternative intermolecular liganding mode. J Biol Chem 1994;269:16041–16045.

    PubMed  CAS  Google Scholar 

  175. Faruqi TR, Weiss EJ, Shapiro MJ, Huang W, Coughlin SR. Structure-function analysis of protease-activated receptor 4 tethered ligand peptides. Determinants of specificity and utility in assays of receptor function. J Biol Chem 2000;275:19728–19734.

    PubMed  CAS  Google Scholar 

  176. Furman MI, Liu L, Benoit SE, Becker RC, Barnard MR, Michelson AD. The cleaved peptide of the thrombin receptor is a strong platelet agonist. Proc Natl Acad Sci USA 1998;95:3082–3087.

    PubMed  CAS  Google Scholar 

  177. Rasmussen UB, Vouret-Craviari V, Jallet S, et al. CDNA clonging and expression of a hamster α-thrombin receptor coupled to Ca2+ mobilization. FEBS Lett 1991;288:123–128.

    PubMed  CAS  Google Scholar 

  178. Ishihara H, Connolly AJ, Zeng D, et al. Protease-activated receptor 3 is a second thrombin receptor in humans. Nature 1997;386:502–506.

    PubMed  CAS  Google Scholar 

  179. Xu W-F, Andersen H, Whitmore TE, et al. Cloning and characterization of human protease-activated receptor 4. Proc Natl Acad Sci USA 1998;95:6642–6646.

    PubMed  CAS  Google Scholar 

  180. Nystedt S, Emilsson K, Wahlestedt C, Sundelin J. Molecular cloning of a potential proteinase activated receptor. Proc Natl Acad Sci 1994;91:9208–9212.

    PubMed  CAS  Google Scholar 

  181. Molino M, Barnathan ES, Numerof R, et al. Interactions of mast cell tryptase with thrombin receptors and PAR-2. J Biol Chem 1997;272:4043–4049.

    PubMed  CAS  Google Scholar 

  182. Camerer E, Huang W, Coughlin SR. Tissue factor-and factor X-dependent activation of PAR2 by factor VIIa. Proc Natl Acad Sci USA 2000;97:5255–5260.

    PubMed  CAS  Google Scholar 

  183. Nystedt S, Emilsson K, Larsson AK, Strombeck B, Sundelin J. Molecular cloning and functional expression of the gene encoding the human proteinase-activated receptor 2. Eur J Biochem 1995;232:84–89.

    PubMed  CAS  Google Scholar 

  184. Mirza H, Schmidt V, Derian C, Jesty J, Bahou WF. Mitogenic responses mediated through the proteinase activated receptor 2 are induced by mast cell α-and β-tryptases. Blood 1997;90:3914–3922.

    PubMed  CAS  Google Scholar 

  185. Cupit LD, Schmidt VA, Bahou WF. Proteolytically activated receptor-3. A member of an emerging gene family of protease receptors expressed on vascular endothelial cells and platelets. Trends Cardiovasc Med 1999;9:42–48.

    PubMed  CAS  Google Scholar 

  186. Steinhoff M, Vergnolle N, Young S, et al. Agonists of proteinase-activated receptor 2 induce inflammation by a neurogenic mechanism. Nat Med 2000;6:151–158.

    PubMed  CAS  Google Scholar 

  187. Kahn ML, Nakanishi-Matsui M, Shapiro MJ, Ishihara H, Coughlin SR. Protease-activated receptors 1 and 4 mediate activation of human platelets by thrombin. J Clin Invest 1999;103:879–887.

    PubMed  CAS  Google Scholar 

  188. Covic L, gresser al, kuliopulos a. Biphasic kinetics of activation and signaling for PAR1 and PAR4 thrombin receptors in platelets. Biochemistry 2000;39:5458–5467.

    PubMed  CAS  Google Scholar 

  189. Bahou WF, Coller BS, Potter CL, Norton KJ, Kutok JL, Goligorsky MS. The thrombin receptor extracellular domain contains sites crucial for peptide ligand-induced activation. J Clin Invest 1993;91:1405–1413.

    Article  PubMed  CAS  Google Scholar 

  190. Brass LF, Manning DR, Cichowski K, Abrams C. Signaling through G proteins in platelets to the integrins and beyond. Thromb Haemost 1997;78:582–589.

    Google Scholar 

  191. Kramer RM, Roberts EF, Um SL, et al. p38 mitogen-activated protein kinase phosphorylates cytosolic phospholipase A2 (cPLA2) in thrombin-stimulated platelets. Evidence that proline-directed phosphorylation is not required for mobilization of arachidonic acid by cPLA2. J Biol Chem 1996;271:27723–27729.

    PubMed  CAS  Google Scholar 

  192. O’Brien PJ, Prevost N, Molino M, et al. Thrombin responses in human endothelial cells. Contributions from receptors other than PAR1 include the transactivation of PAR2 by thrombin-cleaved PAR1. J Biol Chem 2000;275:13502–13509.

    PubMed  CAS  Google Scholar 

  193. Bernatowicz M, Klimas C, Hartl K, Peluso M, Alegretto N, Seiler SM. Development of potent thrombin receptor antagonist peptides. J Med Chem 1996;39:4879–4887.

    PubMed  CAS  Google Scholar 

  194. Andrade-Gordon P, Maryanoff BE, Derian CK, et al. Design, synthesis, and biological characterization of a peptide-mimetic antagonist for a tethered-ligand receptor. Proc Natl Acad Sci USA 1999; 96:12257–12262.

    PubMed  CAS  Google Scholar 

  195. Maeda H, Inazu T, Nagau K, Maruyama S, Nakagawara G, Yamamura H. Possible involvement of protein-tyrosine kinases such as p72SYK in the disc-sphere change response of porcine platelets. J Biochem 1995;17:1201–1208.

    Google Scholar 

  196. Yamamoto H, Vreys I, Stassen JM, Yoshimoto R, Vermylen J, Hoylaerts MF. Antagonism of vWF inhibits both injury induced arterial and venous thrombosis in the hamster. Thromb Haemost 1998;79:202–210.

    PubMed  CAS  Google Scholar 

  197. Scarborough RM, Kleiman NS, Philips DR. Platelet glycoprotein IIb/IIa antagonists. What are the relevant issues concerning their pharmacology and clinical use? Circulation 1999;100:437–444.

    PubMed  CAS  Google Scholar 

  198. Ware J, Russell S, Ruggeri ZM. Generation and rescue of a murine model of platelet dysfunction: the Bernard-Soulier Syndrome. Proc Natl Acad Sci USA 2000;97:2803–2808.

    PubMed  CAS  Google Scholar 

  199. Law DA, Nannizzi-Alaimo L, Ministri K, et al. Genetic and pharmacologic analyses of Syk function in αIIbβ3 signaling in platelets. Blood 1999;93:2645–2652.

    PubMed  CAS  Google Scholar 

  200. Soriano P, Montgomery C, Geske R, Bradley A. Targeted disruption of the c-src proto-oncogene leads to osteopetrosis in mice. Cell 1991;64:693–702.

    PubMed  CAS  Google Scholar 

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  1. The Roon Research Center for Atherosclerosis and Thrombosis, Division of Experimental Hemostasis and Thrombosis, Department of Molecular and Experimental Medicine, The Scripps Research Institute, La Jolla, CA

    Brian Savage PhD & Zaverio M. Ruggeri MD

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  1. Department of Cardiology, St. Vincent’s University Hospital, Dublin, Ireland

    Martin Quinn MB BCh BAO, PhD

  2. University College Dublin, Dublin, Ireland

    Desmond Fitzgerald MD, FRCPI, FESC, AAP (Vice President of Research) (Vice President of Research)

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Savage, B., Ruggeri, Z.M. (2005). Platelet Adhesion. In: Quinn, M., Fitzgerald, D. (eds) Platelet Function. Contemporary Cardiology. Humana Press. https://doi.org/10.1007/978-1-59259-917-2_3

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