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Endogenous Inhibitory Mechanisms and the Regulation of Platelet Function

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Platelets and Megakaryocytes

Part of the book series: Methods in Molecular Biology ((MIMB,volume 788))

Abstract

The response of platelets to changes in the immediate environment is always a balance between activatory and inhibitory signals, the cumulative effect of which is either activation or quiescence. This is true of platelets in free flowing blood and of their regulation of haemostasis and thrombosis. In this review, we consider the endogenous inhibitory mechanisms that combine to regulate platelet activation. These include those derived from the endothelium (nitric oxide, prostacyclin, CD39), inhibitory receptors on the surface of platelets (platelet endothelial cell adhesion molecule-1, carcinoembryonic antigen cell adhesion molecule 1, G6b-B – including evidence for the role of Ig-ITIM superfamily members in the negative regulation of ITAM-associated GPVI platelet–collagen interactions and GPCR-mediated signalling and in positive regulation of “outside-in” integrin αIIbβ3-mediated signalling), intracellular inhibitory receptors (retinoic X receptor, glucocorticoid receptor, peroxisome proliferator-activated receptors, liver X receptor), and emerging inhibitory pathways (canonical Wnt signalling, Semaphorin 3A, endothelial cell specific adhesion molecule, and junctional adhesion molecule-A).

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References

  1. Furchgott, R. F., and Zawadzki, J. V. (1980) The obligatory role of endothelial cells in the relaxation of arterial smooth muscle by acetylcholine, Nature 288, 373–376.

    Article  PubMed  CAS  Google Scholar 

  2. Bellamy, T. C., and Garthwaite, J. (2002) The receptor-like properties of nitric oxide-activated soluble guanylyl cyclase in intact cells, Mol Cell Biochem 230, 165–176.

    Article  PubMed  CAS  Google Scholar 

  3. Munzel, T., Feil, R., Mulsch, A., Lohmann, S. M., Hofmann, F., and Walter, U. (2003) Physiology and pathophysiology of vascular signaling controlled by guanosine 3′,5′-cyclic monophosphate-dependent protein kinase, Circulation 108, 2172–2183.

    Article  PubMed  Google Scholar 

  4. Eigenthaler, M., Ullrich, H., Geiger, J., Horstrup, K., Honig-Liedl, P., Wiebecke, D., and Walter, U. (1993) Defective nitrovasodilator-stimulated protein phosphorylation and calcium regulation in cGMP-dependent protein kinase-deficient human platelets of chronic myelocytic leukemia, J Biol Chem 268, 13526–13531.

    PubMed  CAS  Google Scholar 

  5. Tsudo, M., Kozak, R. W., Goldman, C. K., and Waldmann, T. A. (1987) Contribution of a p75 interleukin 2 binding peptide to a high-affinity interleukin 2 receptor complex, Proc Natl Acad Sci USA 84, 4215–4218.

    Article  PubMed  CAS  Google Scholar 

  6. Eigenthaler, M., Nolte, C., Halbrugge, M., and Walter, U. (1992) Concentration and regulation of cyclic nucleotides, cyclic-nucleotide-dependent protein kinases and one of their major substrates in human platelets. Estimating the rate of cAMP-regulated and cGMP-regulated protein phosphorylation in intact cells, Eur J Biochem 205, 471–481.

    CAS  Google Scholar 

  7. Maurice, D. H., and Haslam, R. J. (1990) Molecular basis of the synergistic inhibition of platelet function by nitrovasodilators and activators of adenylate cyclase: inhibition of cyclic AMP breakdown by cyclic GMP, Mol Pharmacol 37, 671–681.

    PubMed  CAS  Google Scholar 

  8. Nolte, C., Eigenthaler, M., Horstrup, K., Honig-Liedl, P., and Walter, U. (1994) Synergistic phosphorylation of the focal adhesion-associated vasodilator-stimulated phosphoprotein in intact human platelets in response to cGMP- and cAMP-elevating platelet inhibitors, Biochem Pharmacol 48, 1569–1575.

    Article  PubMed  CAS  Google Scholar 

  9. Jensen, B. O., Selheim, F., Doskeland, S. O., Gear, A. R., and Holmsen, H. (2004) Protein kinase A mediates inhibition of the thrombin-induced platelet shape change by nitric oxide, Blood 104, 2775–2782.

    Article  PubMed  CAS  Google Scholar 

  10. Cavallini, L., Coassin, M., Borean, A., and Alexandre, A. (1996) Prostacyclin and sodium nitroprusside inhibit the activity of the platelet inositol 1,4,5-trisphosphate receptor and promote its phosphorylation, J Biol Chem 271, 5545–5551.

    Article  PubMed  CAS  Google Scholar 

  11. Mullershausen, F., Friebe, A., Feil, R., Thompson, W. J., Hofmann, F., and Koesling, D. (2003) Direct activation of PDE5 by cGMP: long-term effects within NO/cGMP signaling, J Cell Biol 160, 719–727.

    Article  PubMed  CAS  Google Scholar 

  12. Butt, E., Abel, K., Krieger, M., Palm, D., Hoppe, V., Hoppe, J., and Walter, U. (1994) cAMP- and cGMP-dependent protein kinase phosphorylation sites of the focal adhesion vasodilator-stimulated phosphoprotein (VASP) in vitro and in intact human platelets, J Biol Chem 269, 14509–14517.

    PubMed  CAS  Google Scholar 

  13. Waldmann, R., Nieberding, M., and Walter, U. (1987) Vasodilator-stimulated protein phosphorylation in platelets is mediated by cAMP- and cGMP-dependent protein kinases, Eur J Biochem 167, 441–448.

    Article  PubMed  CAS  Google Scholar 

  14. Miura, Y., Kaibuchi, K., Itoh, T., Corbin, J. D., Francis, S. H., and Takai, Y. (1992) Phosphorylation of smg p21B/rap1B p21 by cyclic GMP-dependent protein kinase, FEBS Lett 297, 171–174.

    Article  PubMed  CAS  Google Scholar 

  15. Danielewski, O., Schultess, J., and Smolenski, A. (2005) The NO/cGMP pathway inhibits Rap 1 activation in human platelets via cGMP-dependent protein kinase I, Thromb Haemost 93, 319–325.

    PubMed  CAS  Google Scholar 

  16. Reid, H. M., and Kinsella, B. T. (2003) The alpha, but not the beta, isoform of the human thromboxane A2 receptor is a target for nitric oxide-mediated desensitization. Independent modulation of Tp alpha signaling by nitric oxide and prostacyclin, J Biol Chem 278, 51190–51202.

    CAS  Google Scholar 

  17. Sase, K., and Michel, T. (1995) Expression of constitutive endothelial nitric oxide synthase in human blood platelets., Life Sciences, 2049–2055.

    Google Scholar 

  18. Mehta, J. L., Chen, L. Y., Kone, B. C., Mehta, P., and Turner, P. (1995) Identification of constitutive and inducible forms of nitric oxide synthase in human platelets., J Lab Clin Med 125, 370–377.

    PubMed  CAS  Google Scholar 

  19. Freedman, J. E., Loscalzo, J., Barnard, M. R., Alpert, C., Keaney, J. F., and Michelson, A. D. (1997) Nitric oxide released from activated platelets inhibits platelet recruitment, J Clin Invest 100, 350–356.

    Article  PubMed  CAS  Google Scholar 

  20. Malinski, T., Radomski, M. W., Taha, Z., and Moncada, S. (1993) Direct electrochemical measurement of nitric oxide released from human platelets, Biochem Biophys Res Commun 194, 960–965.

    Article  PubMed  CAS  Google Scholar 

  21. Lantoine, F., Brunet, A., Bedioui, F., Devynck, J., and Devynck, M. A. (1995) Direct measurement of nitric oxide production in platelets: relationship with cytosolic Ca2+ concentration, Biochem Biophys Res Commun 215, 842–848.

    Article  PubMed  CAS  Google Scholar 

  22. Riba, R., Sharifi, M., Farndale, R. W., and Naseem, K. M. (2005) Regulation of platelet guanylyl cyclase by collagen: evidence that Glycoprotein VI mediates platelet nitric oxide synthesis in response to collagen, Thromb Haemost 94, 395–403.

    PubMed  CAS  Google Scholar 

  23. Stojanovic, A., Marjanovic, J. A., Brovkovych, V. M., Peng, X., Hay, N., Skidgel, R. A., and Du, X. (2006) A phosphoinositide 3-kinase-AKT-nitric oxide-cGMP signaling pathway in stimulating platelet secretion and aggregation, J Biol Chem 281, 16333–16339.

    Article  PubMed  CAS  Google Scholar 

  24. Riba, R., Oberprieler, N. G., Roberts, W., and Naseem, K. M. (2006) Von Willebrand factor activates endothelial nitric oxide synthase in blood platelets by a glycoprotein Ib-dependent mechanism, J Thromb Haemost 4, 2636–2644.

    Article  PubMed  CAS  Google Scholar 

  25. Morrell, C. N., Matsushita, K., Chiles, K., Scharpf, R. B., Yamakuchi, M., Mason, R. J., Bergmeier, W., Mankowski, J. L., Baldwin, W. M., 3 rd, Faraday, N., and Lowenstein, C. J. (2005) Regulation of platelet granule exocytosis by S-nitrosylation, Proc Natl Acad Sci USA 102, 3782–3787.

    Article  PubMed  CAS  Google Scholar 

  26. Radomski, M. W., Palmer, R. M., and Moncada, S. (1990) An L-arginine/nitric oxide pathway present in human platelets regulates aggregation, Proc Natl Acad Sci USA 87, 5193–5197.

    Article  PubMed  CAS  Google Scholar 

  27. Radomski, M. W., Palmer, R. M., and Moncada, S. (1990) Characterization of the L-arginine:nitric oxide pathway in human platelets, Br J Pharmacol 101, 325–328.

    PubMed  CAS  Google Scholar 

  28. Storey, R. F., and Heptinstall, S. (1999) Laboratory investigation of platelet function, Clin Lab Haematol 21, 317–329.

    Article  PubMed  CAS  Google Scholar 

  29. Williams, R. H., and Nollert, M. U. (2004) Platelet-derived NO slows thrombus growth on a collagen type III surface, Thromb J 2, 11.

    Article  PubMed  CAS  Google Scholar 

  30. Li, W., Mital, S., Ojaimi, C., Csiszar, A., Kaley, G., and Hintze, T. H. (2004) Premature death and age-related cardiac dysfunction in male eNOS-knockout mice, J Mol Cell Cardiol 37, 671–680.

    Article  PubMed  CAS  Google Scholar 

  31. Iafrati, M. D., Vitseva, O., Tanriverdi, K., Blair, P., Rex, S., Chakrabarti, S., Varghese, S., and Freedman, J. E. (2005) Compensatory mechanisms influence hemostasis in setting of eNOS deficiency, Am J Physiol Heart Circ Physiol 288, H1627-1632.

    Article  PubMed  CAS  Google Scholar 

  32. Freedman, J. E., Sauter, R., Battinelli, E. M., Ault, K., Knowles, C., Huang, P. L., and Loscalzo, J. (1999) Deficient platelet-derived nitric oxide and enhanced hemostasis in mice lacking the NOSIII gene, Circ Res 84, 1416–1421.

    PubMed  CAS  Google Scholar 

  33. Gambaryan, S., Kobsar, A., Hartmann, S., Birschmann, I., Kuhlencordt, P. J., Muller-Esterl, W., Lohmann, S. M., and Walter, U. (2008) NO-synthase-/NO-independent regulation of human and murine platelet soluble guanylyl cyclase activity, J Thromb Haemost 6, 1376–1384.

    Article  PubMed  CAS  Google Scholar 

  34. Naseem, K. M., and Riba, R. (2008) Unresolved roles of platelet nitric oxide synthase, J Thromb Haemost 6, 10–19.

    Article  PubMed  CAS  Google Scholar 

  35. Naseem, K. M. (2008) eNOS, iNOS or no NOS, that is the question!, J Thromb Haemost 6, 1373–1375.

    Article  PubMed  CAS  Google Scholar 

  36. Marcondes, S., Cardoso, M. H., Morganti, R. P., Thomazzi, S. M., Lilla, S., Murad, F., De Nucci, G., and Antunes, E. (2006) Cyclic GMP-independent mechanisms contribute to the inhibition of platelet adhesion by nitric oxide donor: a role for alpha-actinin nitration, Proc Natl Acad Sci USA 103, 3434–3439.

    Article  PubMed  CAS  Google Scholar 

  37. Oberprieler, N. G., Roberts, W., Riba, R., Graham, A. M., Homer-Vanniasinkam, S., and Naseem, K. M. (2007) cGMP-independent inhibition of integrin alphaIIbbeta3-mediated platelet adhesion and outside-in signalling by nitric oxide, FEBS Lett 581, 1529–1534.

    Article  PubMed  CAS  Google Scholar 

  38. Shah, C. M., Bell, S. E., Locke, I. C., Chowdrey, H. S., and Gordge, M. P. (2007) Interactions between cell surface protein disulphide isomerase and S-nitrosoglutathione during nitric oxide delivery, Nitric Oxide 16, 135–142.

    Article  PubMed  CAS  Google Scholar 

  39. Gordge, M. P., Hothersall, J. S., and Noronha-Dutra, A. A. (1998) Evidence for a cyclic GMP-independent mechanism in the anti-platelet action of S-nitrosoglutathione, Br J Pharmacol 124, 141–148.

    Article  CAS  PubMed  Google Scholar 

  40. Crane, M. S., Rossi, A. G., and Megson, I. L. (2005) A potential role for extracellular nitric oxide generation in cGMP-independent inhibition of human platelet aggregation: biochemical and pharmacological considerations, Br J Pharmacol 144, 849–859.

    Article  PubMed  CAS  Google Scholar 

  41. Tsikas, D., Ikic, M., Tewes, K. S., Raida, M., and Frolich, J. C. (1999) Inhibition of platelet aggregation by S-nitroso-cysteine via cGMP-independent mechanisms: evidence of inhibition of thromboxane A2 synthesis in human blood platelets, FEBS Lett 442, 162–166.

    Article  PubMed  CAS  Google Scholar 

  42. Dangel, O., Mergia, E., Karlisch, K., Groneberg, D., Koesling, D., and Friebe, A. (2010) Nitric oxide-sensitive guanylyl cyclase is the only nitric oxide receptor mediating platelet inhibition, J Thromb Haemost 8, 1343–1352.

    Article  PubMed  CAS  Google Scholar 

  43. Radomski, M. W., Palmer, R. M., and Moncada, S. (1987) The role of nitric oxide and cGMP in platelet adhesion to vascular endothelium, Biochem Biophys Res Commun 148, 1482–1489.

    Article  PubMed  CAS  Google Scholar 

  44. Radomski, M. W., Palmer, R. M., and Moncada, S. (1987) The anti-aggregating properties of vascular endothelium: interactions between prostacyclin and nitric oxide, Br J Pharmacol 92, 639–646.

    PubMed  CAS  Google Scholar 

  45. Lidbury, P. S., Antunes, E., de Nucci, G., and Vane, J. R. (1989) Interactions of iloprost and sodium nitroprusside on vascular smooth muscle and platelet aggregation, Br J Pharmacol 98, 1275–1280.

    PubMed  CAS  Google Scholar 

  46. Weksler, B. B., Marcus, A. J., and Jaffe, E. A. (1977) Synthesis of prostaglandin I2 (prostacyclin) by cultured human and bovine endothelial cells, Proc Natl Acad Sci USA 74, 3922–3926.

    Article  PubMed  CAS  Google Scholar 

  47. Ingerman-Wojenski, C., Silver, M. J., Smith, J. B., and Macarak, E. (1981) Bovine endothelial cells in culture produce thromboxane as well as prostacyclin, J Clin Invest 67, 1292–1296.

    Article  PubMed  CAS  Google Scholar 

  48. Moncada, S., Gryglewski, R., Bunting, S., and Vane, J. R. (1976) An enzyme isolated from arteries transforms prostaglandin endoperoxides to an unstable substance that inhibits platelet aggregation, Nature 263, 663–665.

    Article  PubMed  CAS  Google Scholar 

  49. Gryglewski, R. J., Bunting, S., Moncada, S., Flower, R. J., and Vane, J. R. (1976) Arterial walls are protected against deposition of platelet thrombi by a substance (prostaglandin X) which they make from prostaglandin endoperoxides, Prostaglandins 12, 685–713.

    Article  PubMed  CAS  Google Scholar 

  50. Needleman, P., Turk, J., Jakschik, B. A., Morrison, A. R., and Lefkowith, J. B. (1986) Arachidonic acid metabolism, Annu Rev Biochem 55, 69–102.

    Article  PubMed  CAS  Google Scholar 

  51. Hamberg, M., Svensson, J., and Samuelsson, B. (1975) Thromboxanes: a new group of biologically active compounds derived from prostaglandin endoperoxides, Proc Natl Acad Sci USA 72, 2994–2998.

    Article  PubMed  CAS  Google Scholar 

  52. FitzGerald, G. A. (1991) Mechanisms of platelet activation: thromboxane A2 as an amplifying signal for other agonists, Am J Cardiol 68, 11B-15B.

    Article  PubMed  CAS  Google Scholar 

  53. Marnett, L. J., Rowlinson, S. W., Goodwin, D. C., Kalgutkar, A. S., and Lanzo, C. A. (1999) Arachidonic acid oxygenation by COX-1 and COX-2. Mechanisms of catalysis and inhibition, J Biol Chem 274, 22903–22906.

    CAS  Google Scholar 

  54. Smith, W. L., DeWitt, D. L., and Garavito, R. M. (2000) Cyclooxygenases: structural, ­cellular, and molecular biology, Annu Rev Biochem 69, 145–182.

    Article  PubMed  CAS  Google Scholar 

  55. Patrignani, P., Sciulli, M. G., Manarini, S., Santini, G., Cerletti, C., and Evangelista, V. (1999) COX-2 is not involved in thromboxane biosynthesis by activated human platelets, J Physiol Pharmacol 50, 661–667.

    PubMed  CAS  Google Scholar 

  56. Spisni, E., Bartolini, G., Orlandi, M., Belletti, B., Santi, S., and Tomasi, V. (1995) Prostacyclin (PGI2) synthase is a constitutively expressed enzyme in human endothelial cells, Exp Cell Res 219, 507–513.

    Article  PubMed  CAS  Google Scholar 

  57. Smith, W. L., DeWitt, D. L., and Allen, M. L. (1983) Bimodal distribution of the prostaglandin I2 synthase antigen in smooth muscle cells, J Biol Chem 258, 5922–5926.

    PubMed  CAS  Google Scholar 

  58. Needleman, P., Moncada, S., Bunting, S., Vane, J. R., Hamberg, M., and Samuelsson, B. (1976) Identification of an enzyme in platelet microsomes which generates thromboxane A2 from prostaglandin endoperoxides, Nature 261, 558–560.

    Article  PubMed  CAS  Google Scholar 

  59. Hsu, P. Y., Tsai, A. L., Kulmacz, R. J., and Wang, L. H. (1999) Expression, purification, and spectroscopic characterization of human thromboxane synthase, J Biol Chem 274, 762–769.

    Article  PubMed  CAS  Google Scholar 

  60. Dutta-Roy, A. K., and Sinha, A. K. (1987) Purification and properties of prostaglandin E1/prostacyclin receptor of human blood platelets, J Biol Chem 262, 12685–12691.

    PubMed  CAS  Google Scholar 

  61. Tsai, A. L., Hsu, M. J., Vijjeswarapu, H., and Wu, K. K. (1989) Solubilization of prostacyclin membrane receptors from human platelets, J Biol Chem 264, 61–67.

    PubMed  CAS  Google Scholar 

  62. Jones, R. L., Qian, Y., Wong, H. N., Chan, H., and Yim, A. P. (1997) Prostanoid action on the human pulmonary vascular system, Clin Exp Pharmacol Physiol 24, 969–972.

    Article  PubMed  CAS  Google Scholar 

  63. Tateson, J. E., Moncada, S., and Vane, J. R. (1977) Effects of prostacyclin (PGX) on cyclic AMP concentrations in human platelets, Prostaglandins 13, 389–397.

    Article  PubMed  CAS  Google Scholar 

  64. Gorman, R. R., Bunting, S., and Miller, O. V. (1977) Modulation of human platelet adenylate cyclase by prostacyclin (PGX), Prostaglandins 13, 377–388.

    Article  PubMed  CAS  Google Scholar 

  65. Kobayashi, T., Ushikubi, F., and Narumiya, S. (2000) Amino acid residues conferring ligand binding properties of prostaglandin I and prostaglandin D receptors. Identification by site-directed mutagenesis, J Biol Chem 275, 24294–24303.

    CAS  Google Scholar 

  66. Siess, W. (1989) Molecular mechanisms of platelet activation, Physiol Rev 69, 58–178.

    PubMed  CAS  Google Scholar 

  67. Armstrong, R. A. (1996) Platelet prostanoid receptors, Pharmacol Ther 72, 171–191.

    Article  PubMed  CAS  Google Scholar 

  68. Robson, S. C., Sevigny, J., and Zimmermann, H. (2006) The E-NTPDase family of ectonucleotidases: Structure function relationships and pathophysiological significance, Purinergic Signal 2, 409–430.

    Article  PubMed  CAS  Google Scholar 

  69. Kansas, G. S., Wood, G. S., and Tedder, T. F. (1991) Expression, distribution, and biochemistry of human CD39. Role in activation-associated homotypic adhesion of lymphocytes, J Immunol 146, 2235–2244.

    CAS  Google Scholar 

  70. Marcus, A. J., Broekman, M. J., Drosopoulos, J. H., Islam, N., Alyonycheva, T. N., Safier, L. B., Hajjar, K. A., Posnett, D. N., Schoenborn, M. A., Schooley, K. A., Gayle, R. B., and Maliszewski, C. R. (1997) The endothelial cell ecto-ADPase responsible for inhibition of platelet function is CD39, J Clin Invest 99, 1351–1360.

    Article  PubMed  CAS  Google Scholar 

  71. Koziak, K., Sevigny, J., Robson, S. C., Siegel, J. B., and Kaczmarek, E. (1999) Analysis of CD39/ATP diphosphohydrolase (ATPDase) expression in endothelial cells, platelets and leukocytes, Thromb Haemost 82, 1538–1544.

    PubMed  CAS  Google Scholar 

  72. Plesner, L. (1995) Ecto-ATPases: identities and functions, Int Rev Cytol 158, 141–214.

    Article  PubMed  CAS  Google Scholar 

  73. Marcus, A. J., Safier, L. B., Hajjar, K. A., Ullman, H. L., Islam, N., Broekman, M. J., and Eiroa, A. M. (1991) Inhibition of platelet function by an aspirin-insensitive endothelial cell ADPase. Thromboregulation by endothelial cells, J Clin Invest 88, 1690–1696.

    CAS  Google Scholar 

  74. Zimmermann, H. (1992) 5′-Nucleotidase: molecular structure and functional aspects, Biochem J 285 ( Pt 2), 345–365.

    PubMed  CAS  Google Scholar 

  75. Dwyer, K. M., Robson, S. C., Nandurkar, H. H., Campbell, D. J., Gock, H., Murray-Segal, L. J., Fisicaro, N., Mysore, T. B., Kaczmarek, E., Cowan, P. J., and d’Apice, A. J. (2004) Thromboregulatory manifestations in human CD39 transgenic mice and the implications for thrombotic disease and transplantation, J Clin Invest 113, 1440–1446.

    Google Scholar 

  76. Marcus, A. J., Broekman, M. J., Drosopoulos, J. H., Islam, N., Pinsky, D. J., Sesti, C., and Levi, R. (2003) Heterologous cell-cell interactions: thromboregulation, cerebroprotection and cardioprotection by CD39 (NTPDase-1), J Thromb Haemost 1, 2497–2509.

    Article  PubMed  CAS  Google Scholar 

  77. Burnstock, G. (2002) Purinergic signaling and vascular cell proliferation and death, Arterioscler Thromb Vasc Biol 22, 364–373.

    Article  PubMed  CAS  Google Scholar 

  78. Jackson, D. E., Ward, C. M., Wang, R., and Newman, P. J. (1997) The protein-tyrosine phosphatase SHP-2 binds platelet/endothelial cell adhesion molecule-1 (PECAM-1) and forms a distinct signaling complex during platelet aggregation, J. Biol. Chem. 272, 6986–6993.

    Article  PubMed  CAS  Google Scholar 

  79. Newman, P. J. (1999) Switched at birth: a new family for PECAM-1, J Clin Invest 103, 5–9.

    Article  PubMed  CAS  Google Scholar 

  80. Gibbins, J. M. (2002) The negative regulation of platelet function: extending the role of the ITIM, Trends Cardiovasc Med 12, 213–219.

    Article  PubMed  CAS  Google Scholar 

  81. Wong, C., Liu, Y., Yip, J., Chand, R., Wee, J. L., Oates, L., Nieswandt, B., Reheman, A., Ni, H., Beauchemin, N., and Jackson, D. E. (2009) CEACAM1 negatively regulates platelet-collagen interactions and thrombus growth in vitro and in vivo, Blood 113, 1818–1828.

    Article  PubMed  CAS  Google Scholar 

  82. Newland, S. A., Macaulay, I. C., Floto, R. A., de Vet, E. C., Ouwehand, W. H., Watkins, N. A., Lyons, P. A., and Campbell, R. D. (2007) The novel inhibitory receptor G6B is expressed on the surface of platelets and attenuates platelet function in vitro, Blood 109, 4806–4809.

    Article  PubMed  CAS  Google Scholar 

  83. Senis, Y. A., Tomlinson, M. G., Garcia, A., Dumon, S., Heath, V. L., Herbert, J., Cobbold, S. P., Spalton, J. C., Ayman, S., Antrobus, R., Zitzmann, N., Bicknell, R., Frampton, J., Authi, K. S., Martin, A., and Wakelam, M. J. O. (2007) A comprehensive proteomics and genomics analysis reveals novel transmembrane proteins in human platelets and mouse megakaryocytes including G6b-B, a novel immunoreceptor tyrosine-based inhibitory motif protein, Molecular & Cellular Proteomics 6, 548–564.

    Article  CAS  Google Scholar 

  84. Mori, J., Pearce, A. C., Spalton, J. C., Grygielska, B., Eble, J. A., Tomlinson, M. G., Senis, Y. A., and Watson, S. P. (2008) G6b-B Inhibits Constitutive and Agonist-induced Signaling by Glycoprotein VI and CLEC-2, Journal of Biological Chemistry 283, 35419–35427.

    Article  PubMed  CAS  Google Scholar 

  85. Macaulay, I. C., Tijssen, M. R., Thijssen-Timmer, D. C., Gusnanto, A., Steward, M., Burns, P., Langford, C. F., Ellis, P. D., Dudbridge, F., Zwaginga, J. J., Watkins, N. A., van der Schoot, C. E., and Ouwehand, W. H. (2007) Comparative gene expression profiling of in vitro differentiated megakaryocytes and erythroblasts identifies novel activatory and inhibitory platelet membrane proteins, Blood 109, 3260–3269.

    Article  PubMed  CAS  Google Scholar 

  86. Newman, P. J., Berndt, M. J., Gorski, J., White, G. C., Lyman, S., Paddock, C., and Muller, W. A. (1990) PECAM-1 (CD31) cloning and relation to adhesion molecules of the immunoglobulin gene superfamily., Science 247, 1219–1222.

    Article  PubMed  CAS  Google Scholar 

  87. Kirschbaum, N. E., Gumina, R. J., and Newman, P. J. (1994) Organization of the gene for human platelet/endothelial cell adhesion molecule-1 shows alternatively spliced isoforms and a functionally complex cytoplasmic domain, Blood 84, 4028–4037.

    PubMed  CAS  Google Scholar 

  88. Ohto, H., Maeda, H., Shibata, Y., Chen, R. F., Ozaki, Y., Higashihara, M., Takeuchi, A., and Tohyama, H. (1985) A novel leukocyte differentiation antigen: two monoclonal antibodies TM2 and TM3 define a 120-kd molecule present on neutrophils, monocytes, platelets, and activated lymphoblasts, Blood 66, 873–881.

    PubMed  CAS  Google Scholar 

  89. Goyert, S. M., Ferrero, E. M., Seremetis, S. V., Winchester, R. J., Silver, J., and Mattison, A. C. (1986) Biochemistry and expression of myelomonocytic antigens, J Immunol 137, 3909–3914.

    PubMed  CAS  Google Scholar 

  90. Lyons, A. B., Cooper, S. J., Cole, S. R., and Ashman, L. K. (1988) Human myeloid differentiation antigens identified by monoclonal antibodies to the myelomonocytic leukemia cell line RC-2A, Pathology 20, 137–146.

    Article  PubMed  CAS  Google Scholar 

  91. Cabanas, C., Sanchez-Madrid, F., Bellon, T., Figdor, C. G., Te Velde, A. A., Fernandez, J. M., Acevedo, A., and Bernabeu, C. (1989) Characterization of a novel myeloid antigen regulated during differentiation of monocytic cells, Eur J Immunol 19, 1373–1378.

    Article  PubMed  CAS  Google Scholar 

  92. Newman, P. J. (1994) The role of PECAM-1 in vascular cell biology, Ann N Y Acad Sci 714, 165–174.

    Article  PubMed  CAS  Google Scholar 

  93. Wu, X. W., and Lian, E. C. (1997) Binding properties and inhibition of platelet aggregation by a monoclonal antibody to CD31 (PECAM-1), Arterioscler Thromb Vasc Biol 17, 3154–3158.

    Article  PubMed  CAS  Google Scholar 

  94. Metzelaar, M. J., Korteweg, J., Sixma, J. J., and Nieuwenhuis, H. K. (1991) Biochemical characterization of PECAM-1 (CD31 antigen) on human platelets, Thromb Haemost 66, 700–707.

    PubMed  CAS  Google Scholar 

  95. Mazurov, A. V., Vinogradov, D. V., Kabaeva, N. V., Antonova, G. N., Romanov, Y. A., Vlasik, T. N., Antonov, A. S., and Smirnov, V. N. (1991) A monoclonal antibody, VM64, reacts with a 130 kDa glycoprotein common to platelets and endothelial cells: heterogeneity in antibody binding to human aortic endothelial cells, Thromb Haemost 66, 494–499.

    PubMed  CAS  Google Scholar 

  96. Cicmil, M., Thomas, J. M., Sage, T., Barry, F. A., Leduc, M., Bon, C., and Gibbins, J. M. (2000) Collagen, Convulxin, and Thrombin Stimulate Aggregation-independent Tyrosine Phosphorylation of CD31 in Platelets. Evidence for the involvement of Src family kinases., J. Biol. Chem. 275, 27339–27347.

    PubMed  CAS  Google Scholar 

  97. Buckley, C. D., Doyonnas, R., Newton, J. P., Blystone, S. D., Brown, E. J., Watt, S. M., and Simmons, D. L. (1996) Identification of avb3 as a heterotypic ligand for CD31/PECAM-1., J.Cell Sci. 109, 437–445.

    CAS  Google Scholar 

  98. Patil, S., Newman, D. K., and Newman, P. J. (2001) Platelet endothelial cell adhesion molecule-1 serves as an inhibitory receptor that modulates platelet responses to collagen, Blood 97, 1727–1732.

    Article  PubMed  CAS  Google Scholar 

  99. Cramer, E. M., Berger, G., and Berndt, M. C. (1994) Platelet alpha-granule and plasma membrane share two new components: CD9 and PECAM-1, Blood 84, 1722–1730.

    PubMed  CAS  Google Scholar 

  100. Jackson, D. E., Kupcho, K. R., and Newman, P. J. (1997) Characterization of Phosphotyrosine Binding Motifs in the Cytoplasmic Domain of Platelet/Endothelial Cell Adhesion Molecule-1 (PECAM-1) that are required for the Cellular Association and Activation of the Protein-tyrosine Phosphatase, SHP-2, J. Biol. Chem. 272, 24868–24875.

    Article  PubMed  CAS  Google Scholar 

  101. Vivier, E., and Daeron, M. (1997) Immunoreceptor tyrosine-based inhibitory motifs., Immunol. Today 18, 286–291.

    CAS  Google Scholar 

  102. Rathore, V., Stapleton, M. A., Hillery, C. A., Montgomery, R. R., Nichols, T. C., Merricks, E. P., Newman, D. K., and Newman, P. J. (2003) PECAM-1 negatively regulates GPIb/V/IX signaling in murine platelets, Blood 102, 3658–3664.

    Article  PubMed  CAS  Google Scholar 

  103. Jones, K. L., Hughan, S. C., Dopheide, S. M., Farndale, R. W., Jackson, S. P., and Jackson, D. E. (2001) Platelet endothelial cell adhesion molecule-1 is a negative regulator of platelet-collagen interactions, Blood 98, 1456–1463.

    Article  PubMed  CAS  Google Scholar 

  104. Cao, M. Y., Huber, M., Beauchemin, N., Famiglietti, J., Albelda, S. M., and Veillette, A. (1998) Regulation of mouse PECAM-1 tyrosine phosphorylation by the Src and Csk families of protein-tyrosine kinases, J Biol Chem 273, 15765–15772.

    Article  PubMed  CAS  Google Scholar 

  105. Chiu, Y. J., McBeath, E., and Fujiwara, K. (2008) Mechanotransduction in an extracted cell model: Fyn drives stretch- and flow-elicited PECAM-1 phosphorylation, J Cell Biol 182, 753–763.

    Article  PubMed  CAS  Google Scholar 

  106. Newman, D. K., Hamilton, C., and Newman, P. J. (2001) Inhibition of antigen-receptor signaling by Platelet Endothelial Cell Adhesion Molecule-1 (CD31) requires functional ITIMs, SHP-2, and p56(lck), Blood 97, 2351–2357.

    Article  PubMed  CAS  Google Scholar 

  107. Hua, C. T., Gamble, J. R., Vadas, M. A., and Jackson, D. E. (1998) Recruitment and Activation of SHP-1 Protein-tyrosine Phosphatase by Human Platelet Endothelial Cell Adhesion Molecule-1 (PECAM-1). Identification of Immunoreceptor Tyrosine-Based Inhibitory Motif-Like Binding Motifs and Substrates, J. Biol. Chem. 273, 28332–28340.

    Article  PubMed  CAS  Google Scholar 

  108. Pumphrey, N. J., Taylor, V. T., Freeman, S., Douglas, M. R., Bradfield, P. F., Young, S. P., Lord, J. M., Wakelam, M. J. O., Bird, I. N., Salmon, M., and Buckley, C. D. (1999) Differetial association of cytoplasmic signalling molecules SHP-1, SHP-2, SHIP and phosphlipase C-γ1 with PECAM-1/CD31, FEBS Lett. 450, 77–83.

    Article  PubMed  CAS  Google Scholar 

  109. Relou, I. A. M., Gorter, G., Ferreira, I. A., van Rijn, H. J. M., and Akkerman, J. W. N. (2003) Platelet endothelial cell adhesion molecule-1 (PECAM-1) inhibits low density lipoprotein-induced signaling in platelets, Journal of Biological Chemistry 278, 32638–32644.

    Article  PubMed  CAS  Google Scholar 

  110. Thai le, M., Ashman, L. K., Harbour, S. N., Hogarth, P. M., and Jackson, D. E. (2003) Physical proximity and functional interplay of PECAM-1 with the Fc receptor Fc gamma RIIa on the platelet plasma membrane, Blood 102, 3637–3645.

    Article  CAS  Google Scholar 

  111. Moraes, L. A., Barrett, N. E., Jones, C. I., Holbrook, L. M., Spyridon, M., Sage, T., Newman, D. K., and Gibbins, J. M. (2010) PECAM-1 regulates collagen-stimulated platelet function by modulating the association of PI3 Kinase with Gab1 and LAT, J Thromb Haemost.

    Google Scholar 

  112. Sardjono, C. T., Harbour, S. N., Yip, J. C., Paddock, C., Tridandapani, S., Newman, P. J., and Jackson, D. E. (2006) Palmitoylation at Cys(595) is essential for PECAM-I localisation into membrane microdomains and for efficient PECAM-I-mediated cytoprotection, Thrombosis and Haemostasis 96, 756–766.

    PubMed  CAS  Google Scholar 

  113. Cicmil, M., Thomas, J. M., Leduc, M., Bon, C., and Gibbins, J. M. (2002) PECAM-1 signalling inhibits the activation of human platelets, Blood 99, 137–144.

    Article  PubMed  CAS  Google Scholar 

  114. Jones, C. I., Garner, S. F., Moraes, L. A., Kaiser, W. J., Rankin, A., Ouwehand, W. H., Goodall, A. H., and Gibbins, J. M. (2009) PECAM-1 expression and activity negatively regulate multiple platelet signaling pathways, FEBS Lett 583, 3618–3624.

    Article  PubMed  CAS  Google Scholar 

  115. Falati, S., Patil S., Gross, P. L., Stapleton, M., Merrill-Skoloff G., Barrett, N. E., Pixton, K. L., Weiler H., Cooley B., Newman D.K., Newman, P. J., Furie, B. C., Furie B., and Gibbins, J. M. (2006) Platelet PECAM-1 inhibits thrombus formation in vivo, Blood 107, 535–541.

    Article  PubMed  CAS  Google Scholar 

  116. Novinska, M. S., Rathoare, V., Newman, D. K., and Newman, P. J. (2007) PECAM-1, Platelets, Chapter 11, pages 221–230.

    Google Scholar 

  117. Gibbins, J., Asselin, J., Farndale, R., Barnes, M., Law, C. L., and Watson, S. P. (1996) Tyrosine phosphorylation of the Fc receptor gamma-chain in collagen-stimulated platelets, J Biol Chem 271, 18095–18099.

    Article  PubMed  CAS  Google Scholar 

  118. Gibbins, J. M., Okuma, M., Farndale, R., Barnes, M., and Watson, S. P. (1997) Glycoprotein VI is the collagen receptor in platelets which underlies tyrosine phosphorylation of the Fc receptor γ-chain, FEBS Letters 413, 255–259.

    Article  PubMed  CAS  Google Scholar 

  119. Poole, A., Gibbins, J. M., Turner, M., vanVugt, M. J., vandeWinkel, J. G. J., Saito, T., Tybulewicz, V. L. J., and Watson, S. P. (1997) The Fc receptor gamma-chain and the tyrosine kinase Syk are essential for activation of mouse platelets by collagen, 16, 2333–2341.

    Google Scholar 

  120. Falati, S., Edmead, C. E., and Poole, A. W. (1999) Glycoprotein Ib-V-IX, a receptor for von Willebrand factor, couples physically and functionally to the Fc receptor gamma- chain, Fyn, and Lyn to activate human platelets, Blood 94, 1648–1656.

    CAS  Google Scholar 

  121. Reth, M. (1989) Antigen receptor tail clue, Nature 338, 383–384.

    Article  PubMed  CAS  Google Scholar 

  122. Odin, J. A., Edberg, J. C., Painter, C. J., Kimberly, R. P., and Unkeless, J. C. (1991) Regulation of phagocytosis and [Ca2+]i flux by distinct regions of an Fc receptor, Science 254, 1785–1788.

    Article  PubMed  CAS  Google Scholar 

  123. Dhanjal, T. S., Ross, E. A., Auger, J. M., McCarty, O. J., Hughes, C. E., Senis, Y. A., Buckley, C. D., and Watson, S. P. (2007) Minimal regulation of platelet activity by PECAM-1, Platelets 18, 56–67.

    Article  PubMed  CAS  Google Scholar 

  124. Wee, J. L., and Jackson, D. E. (2005) The Ig-ITIM superfamily member PECAM-1 regulates the “outside-in” signaling properties of integrin alpha(IIb)beta(3) in platelets, Blood 106, 3816–3823.

    Article  PubMed  CAS  Google Scholar 

  125. Berman, M. E., and Muller, W. A. (1995) Ligation of Platelet Endothelial-Cell Adhesion Molecule-1 (Pecam-1/Cd31) on Monocytes and Neutrophils Increases Binding- Capacity of Leukocyte Cr3 (Cd11b/Cd18), J. Immunol. 154, 299–307.

    PubMed  CAS  Google Scholar 

  126. Berman, M. E., Xie, Y., and Muller, W. A. (1996) Roles of platelet endothelial cell adhesion molecule-1 (PECAM- 1,CD31) in natural killer cell transendothelial migration and beta(2) integrin activation, J. Immunol. 156, 1515–1524.

    PubMed  CAS  Google Scholar 

  127. Chiba, R., Nakagawa, N., Kuroasawa, K., Tanaka, Y., Saito, Y., and Iwamoto, I. (1999) Ligation of CD31(PECAM-1) on endothelial cells increases adhesive function of αvβ3 integrin and enhances b1 integrin mediated ­adhesion of eosinophilis to endothelial cells, Blood 94, 1319–1329.

    PubMed  CAS  Google Scholar 

  128. Pellegatta, F., Chierchia, S. L., and Zocchi, M. R. (1998) Functional association of platelet endothelial cell adhesion molecule-1 and phosphoinositide 3-kinase in human neutrophils, Journal of Biological Chemistry 273, 27768–27771.

    Article  PubMed  CAS  Google Scholar 

  129. Piali, L., Albelda, S. M., Baldwin, H. S., Hammel, P., Gisler, R. H., and Imhof, B. A. (1993) Murine platelet endothelial cell adhesion molecule (PECAM-1/CD31) modulates b2 integrins on lymphokine-activated killer cells., Eur.J.Immunol. 23, 2464–2471.

    Article  PubMed  CAS  Google Scholar 

  130. Tanaka, Y., Albelda, S. M., Horgan, K. J., van Seventer, G. A., Shimizu, Y., Newman, W., Hallam, J., Newman, P. J., Buck, C. A., and Shaw, S. (1992) CD31 expressed on distinctive T cell subsets is a preferential amplifier of b1 integrin-mediated adhesion, J Exp Med 176, 245–253.

    Article  PubMed  CAS  Google Scholar 

  131. Zhao, T. M., and Newman, P. J. (2001) Integrin activation by regulated dimerization and oligomerization of platelet endothelial cell adhesion molecule (PECAM)-1 from within the cell, Journal of Cell Biology 152, 65–73.

    Article  PubMed  CAS  Google Scholar 

  132. Leavesley, D. I., Oliver, J. M., Swart, B. W., Berndt, M. C., Haylock, D. N., and Simmons, P. J. (1994) Signals from Platelet Endothelial-Cell Adhesion Molecule Enhance the Adhesive Activity of the Very Late Antigen-4 Integrin of Human Cd34(+) Hematopoietic Progenitor Cells, J. Immunol. 153, 4673–4683.

    PubMed  CAS  Google Scholar 

  133. Varon, D., Jackson, D. E., Shenkman, B., Dardik, R., Tamarin, I., Savion, N., and Newman, P. J. (1998) Platelet/endothelial cell adhesion molecule-1 serves as a costimulatory agonist receptor that modulates integrin-dependent adhesion and aggregation of human platelets, Blood 91, 500–507.

    PubMed  CAS  Google Scholar 

  134. Reedquist, K. A., Ross, E., Koop, E. A., Wolthuis, R. M. F., Zwartkruis, F. J. T., van Kooyk, Y., Salmon, M., Buckley, C. D., and Bos, J. L. (2000) The small GTPase, Rap1, mediates CD31-induced integrin adhesion, Journal of Cell Biology 148, 1151–1158.

    Article  PubMed  CAS  Google Scholar 

  135. Wilkinson, R., Lyons, A. B., Roberts, D., Wong, M. X., Bartley, P. A., and Jackson, D. E. (2002) Platelet endothelial cell adhesion molecule-1 (PECAM-1/CD31) acts as a regulator of B-cell development, B-cell antigen receptor (BCR)-mediated activation, and autoimmune disease, Blood 100, 184–193.

    Article  PubMed  CAS  Google Scholar 

  136. Gao, C., Sun, W., Christofidou-Solomidou, M., Sawada, M., Newman, D. K., Bergom, C., Albelda, S. M., Matsuyama, S., and Newman, P. J. (2003) PECAM-1 functions as a specific and potent inhibitor of mitochondrial-­dependent apoptosis, Blood 102, 169–179.

    Article  PubMed  CAS  Google Scholar 

  137. Wong, M. X., Roberts, D., Bartley, P. A., and Jackson, D. E. (2002) Absence of platelet endothelial cell adhesion molecule-1 (CD31) leads to increased severity of local and systemic IgE-mediated anaphylaxis and modulation of mast cell activation, J Immunol 168, 6455–6462.

    PubMed  CAS  Google Scholar 

  138. Graesser, D., Solowiej, A., Bruckner, M., Osterweil, E., Juedes, A., Davis, S., Ruddle, N. H., Engelhardt, B., and Madri, J. A. (2002) Altered vascular permeability and early onset of experimental autoimmune encephalomyelitis in PECAM-1-deficient mice, J Clin Invest 109, 383–392.

    PubMed  CAS  Google Scholar 

  139. Albelda, S. M., Muller, W. A., Buck, C. A., and Newman, P. J. (1991) Molecular and cellular properties of PECAM-1 (endoCAM/CD31): a novel vascular cell-cell adhesion molecule, J Cell Biol 114, 1059–1068.

    Article  PubMed  CAS  Google Scholar 

  140. Albelda, S. M., Oliver, P. D., Romer, L. H., and Buck, C. A. (1990) EndoCAM: a novel endothelial cell-cell adhesion molecule, J Cell Biol 110, 1227–1237.

    Article  PubMed  CAS  Google Scholar 

  141. Schimmenti, L. A., Yan, H. C., Madri, J. A., and Albelda, S. M. (1992) Platelet endothelial cell adhesion molecule, PECAM-1, modulates cell migration, J Cell Physiol 153, 417–428.

    Article  PubMed  CAS  Google Scholar 

  142. Muller, W. A., Weigl, S. A., Deng, X., and Phillips, D. M. (1993) PECAM-1 is required for transendothelial migration of leukocytes, J Exp Med 178, 449–460.

    Article  PubMed  CAS  Google Scholar 

  143. DeLisser, H. M., Christofidou-Solomidou, M., Strieter, R. M., Burdick, M. D., Robinson, C. S., Wexler, R. S., Kerr, J. S., Garlanda, C., Merwin, J. R., Madri, J. A., and Albelda, S. M. (1997) Involvement of endothelial PECAM-1/CD31 in angiogenesis, Am J Pathol 151, 671–677.

    PubMed  CAS  Google Scholar 

  144. Chimini, G. (2002) Apoptosis: repulsive encounters, Nature 418, 139–141.

    Article  PubMed  CAS  Google Scholar 

  145. Ferrero, E., Ferrero, M. E., Pardi, R., and Zocchi, M. R. (1995) The platelet endothelial cell adhesion molecule-1 (PECAM1) contributes to endothelial barrier function, FEBS Lett 374, 323–326.

    Article  PubMed  CAS  Google Scholar 

  146. Gratzinger, D., Barreuther, M., and Madri, J. A. (2003) Platelet-endothelial cell adhesion molecule-1 modulates endothelial migration through its immunoreceptor tyrosine-based inhibitory motif, Biochem Biophys Res Commun 301, 243–249.

    Article  PubMed  CAS  Google Scholar 

  147. O’Brien, C. D., Cao, G., Makrigiannakis, A., and DeLisser, H. M. (2004) Role of immunoreceptor tyrosine-based inhibitory motifs of PECAM-1 in PECAM-1-dependent cell migration, Am J Physiol Cell Physiol 287, C1103-1113.

    Article  PubMed  Google Scholar 

  148. Zhu, J. X., Cao, G., Williams, J. T., and Delisser, H. M. (2010) SHP-2 phosphatase activity is required for PECAM-1-dependent cell motility, Am J Physiol Cell Physiol 299, C854-865.

    Article  PubMed  CAS  Google Scholar 

  149. Hansson, M., Odin, P., Johansson, S., and Obrink, B. (1990) Comparison and functional characterization of C-CAM, glycoprotein IIb/IIIa and integrin beta 1 in rat platelets, Thromb Res 58, 61–73.

    Article  PubMed  CAS  Google Scholar 

  150. de Vet, E., Aguado, B., and Campbell, R. D. (2001) G6b, a novel immunoglobulin superfamily member encoded in the human major histocompatibility complex, interacts with SHP-1 and SHP-2, Journal of Biological Chemistry 276, 42070–42076.

    Article  PubMed  Google Scholar 

  151. Ali, F. Y., Davidson, S. J., Moraes, L. A., Traves, S. L., Paul-Clark, M., Bishop-Bailey, D., Warner, T. D., and Mitchell, J. A. (2006) Role of nuclear receptor signaling in platelets: antithrombotic effects of PPARbeta, Faseb J 20, 326–328.

    PubMed  CAS  Google Scholar 

  152. Moraes, L. A., Paul-Clark, M. J., Rickman, A., Flower, R. J., Goulding, N. J., and Perretti, M. (2005) Ligand-specific glucocorticoid receptor activation in human platelets, Blood 106, 4167–4175.

    Article  PubMed  CAS  Google Scholar 

  153. Moraes, L. A., Swales, K. E., Wray, J. A., Damazo, A., Gibbins, J. M., Warner, T. D., and Bishop-Bailey, D. (2007) Nongenomic signaling of the retinoid X receptor through binding and inhibiting Gq in human platelets, Blood 109, 3741–3744.

    Article  PubMed  CAS  Google Scholar 

  154. Spyridon M, Moraes, L. A., Jones, C. I., Sage, T., Sasikumar, P., Bucci, G., and Gibbins, J. M. (2010) LXR as a novel anti-thrombotic target, Under revision.

    Google Scholar 

  155. Akbiyik, F., Ray, D. M., Gettings, K. F., Blumberg, N., Francis, C. W., and Phipps, R. P. (2004) Human bone marrow megakaryocytes and platelets express PPARgamma, and PPARgamma agonists blunt platelet release of CD40 ligand and thromboxanes, Blood 104, 1361–1368.

    Article  PubMed  CAS  Google Scholar 

  156. Ali, F. Y., Davidson, S. J., Moraes, L. A., Traves, S. L., Paul-Clark, M., Bishop-Bailey, D., Warner, T. D., and Mitchell, J. A. (2005) Role of nuclear receptor signaling in platelets: antithrombotic effects of PPAR beta, Faseb Journal 19, 326-  +  .

    Google Scholar 

  157. Moraes, L. A., Spyridon, M., Kaiser, W. J., Jones, C. I., Sage, T., Atherton, R. E. L., and Gibbins, J. M. (2010) Non-genomic effects of PPAR gamma ligands: inhibition of ­GPVI-stimulated platelet activation, J Thromb Haemost 8, 577–587.

    Article  PubMed  CAS  Google Scholar 

  158. Berger, J. P., Akiyama, T. E., and Meinke, P. T. (2005) PPARs: therapeutic targets for metabolic disease, Trends in Pharmacological Sciences 26, 244–251.

    Article  PubMed  CAS  Google Scholar 

  159. Irons, B. K., Greene, R. S., Mazzolini, T. A., Edwards, K. L., and Sleeper, R. B. (2006) Implications of rosiglitazone and pioglitazone on cardiovascular risk in patients with type 2 diabetes mellitus, Pharmacotherapy 26, 168–181.

    Article  PubMed  CAS  Google Scholar 

  160. Marx, N., Duez, H., Fruchart, J. C., and Staels, B. (2004) Peroxisome proliferator-activated receptors and atherogenesis - Regulators of gene expression in vascular cells, Circulation Research 94, 1168–1178.

    Article  PubMed  CAS  Google Scholar 

  161. Moraes, L. A., Piqueras, L., and Bishop-Bailey, D. (2006) Peroxisome proliferator-activated receptors and inflammation, Pharmacol Ther 110, 371–385.

    Article  PubMed  CAS  Google Scholar 

  162. Lee, C. H., Chawla, A., Urbiztondo, N., Liao, D., Boisvert, W. A., Evans, R. M., and Curtiss, L. K. (2003) Transcriptional repression of atherogenic inflammation: modulation by PPARdelta, Science 302, 453–457.

    Article  PubMed  CAS  Google Scholar 

  163. Forman, B. M., Chen, J., and Evans, R. M. (1997) Hypolipidemic drugs, polyunsaturated fatty acids, and eicosanoids are ligands for peroxisome proliferator-activated receptors alpha and delta, Proc Natl Acad Sci USA 94, 4312–4317.

    Article  PubMed  CAS  Google Scholar 

  164. Joseph, S. B., Castrillo, A., Laffitte, B. A., Mangelsdorf, D. J., and Tontonoz, P. (2003) Reciprocal regulation of inflammation and lipid metabolism by liver X receptors, Nature Medicine 9, 213–219.

    Article  PubMed  CAS  Google Scholar 

  165. Joseph, S. B., McKilligin, E., Pei, L. M., Watson, M. A., Collins, A. R., Laffitte, B. A., Chen, M. Y., Noh, G., Goodman, J., Hagger, G. N., Tran, J., Tippin, T. K., Wang, X. P., Lusis, A. J., Hsueh, W. A., Law, R. E., Collins, J. L., Willson, T. M., and Tontonoz, P. (2002) Synthetic LXR ligand inhibits the development of atherosclerosis in mice, Proceedings of the National Academy of Sciences of the United States of America 99, 7604–7609.

    Article  PubMed  CAS  Google Scholar 

  166. Tangirala, R. K., Bischoff, E. D., Joseph, S. B., Wagner, B. L., Walczak, R., Laffitte, B. A., Daige, C. L., Thomas, D., Heyman, R. A., Mangelsdorf, D. J., Wang, X. P., Lusis, A. J., Tontonoz, P., and Schulman, I. G. (2002) Identification of macrophage liver X receptors as inhibitors of atherosclerosis, Proceedings of the National Academy of Sciences of the United States of America 99, 11896–11901.

    Article  PubMed  CAS  Google Scholar 

  167. Goulding, N. J. (2004) The molecular complexity of glucocorticoid actions in inflammation - a four-ring circus, Curr Opin Pharmacol 4, 629–636.

    Article  PubMed  CAS  Google Scholar 

  168. Schaaf, M. J., and Cidlowski, J. A. (2002) Molecular mechanisms of glucocorticoid action and resistance, J Steroid Biochem Mol Biol 83, 37–48.

    Article  PubMed  CAS  Google Scholar 

  169. Huang, H., and He, X. (2008) Wnt/beta-catenin signaling: new (and old) players and new insights, Curr Opin Cell Biol 20, 119–125.

    Article  PubMed  CAS  Google Scholar 

  170. Logan, C. Y., and Nusse, R. (2004) The Wnt signaling pathway in development and disease, Annu Rev Cell Dev Biol 20, 781–810.

    Article  PubMed  CAS  Google Scholar 

  171. Hart, M. J., de los Santos, R., Albert, I. N., Rubinfeld, B., and Polakis, P. (1998) Downregulation of beta-catenin by human Axin and its association with the APC tumor suppressor, beta-catenin and GSK3 beta, Curr Biol 8, 573–581.

    Google Scholar 

  172. Kishida, S., Yamamoto, H., Ikeda, S., Kishida, M., Sakamoto, I., Koyama, S., and Kikuchi, A. (1998) Axin, a negative regulator of the wnt signaling pathway, directly interacts with adenomatous polyposis coli and regulates the stabilization of beta-catenin, J Biol Chem 273, 10823–10826.

    Article  PubMed  CAS  Google Scholar 

  173. Liu, C., Li, Y., Semenov, M., Han, C., Baeg, G. H., Tan, Y., Zhang, Z., Lin, X., and He, X. (2002) Control of beta-catenin phosphorylation/degradation by a dual-kinase mechanism, Cell 108, 837–847.

    Article  PubMed  CAS  Google Scholar 

  174. Yost, C., Torres, M., Miller, J. R., Huang, E., Kimelman, D., and Moon, R. T. (1996) The axis-inducing activity, stability, and subcellular distribution of beta-catenin is regulated in Xenopus embryos by glycogen synthase kinase 3, Genes Dev 10, 1443–1454.

    Article  PubMed  CAS  Google Scholar 

  175. Aberle, H., Bauer, A., Stappert, J., Kispert, A., and Kemler, R. (1997) beta-catenin is a target for the ubiquitin-proteasome pathway, EMBO J 16, 3797–3804.

    Article  PubMed  CAS  Google Scholar 

  176. Latres, E., Chiaur, D. S., and Pagano, M. (1999) The human F box protein beta-Trcp associates with the Cul1/Skp1 complex and regulates the stability of beta-catenin, Oncogene 18, 849–854.

    Article  PubMed  CAS  Google Scholar 

  177. Liu, C., Kato, Y., Zhang, Z., Do, V. M., Yankner, B. A., and He, X. (1999) beta-Trcp couples beta-catenin phosphorylation-degradation and regulates Xenopus axis formation, Proc Natl Acad Sci USA 96, 6273–6278.

    Article  PubMed  CAS  Google Scholar 

  178. Macdonald, B. T., Semenov, M. V., and He, X. (2007) SnapShot: Wnt/beta-catenin signaling, Cell 131, 1204.

    Article  PubMed  CAS  Google Scholar 

  179. Steele, B. M., Harper, M. T., Macaulay, I. C., Morrell, C. N., Perez-Tamayo, A., Foy, M., Habas, R., Poole, A. W., Fitzgerald, D. J., and Maguire, P. B. (2009) Canonical Wnt signaling negatively regulates platelet function, Proc Natl Acad Sci USA 106, 19836–19841.

    PubMed  CAS  Google Scholar 

  180. Takahashi, T., Fournier, A., Nakamura, F., Wang, L. H., Murakami, Y., Kalb, R. G., Fujisawa, H., and Strittmatter, S. M. (1999) Plexin-neuropilin-1 complexes form functional semaphorin-3A receptors, Cell 99, 59–69.

    Article  PubMed  CAS  Google Scholar 

  181. Tamagnone, L., Artigiani, S., Chen, H., He, Z., Ming, G. I., Song, H., Chedotal, A., Winberg, M. L., Goodman, C. S., Poo, M., Tessier-Lavigne, M., and Comoglio, P. M. (1999) Plexins are a large family of receptors for transmembrane, secreted, and GPI-anchored semaphorins in vertebrates, Cell 99, 71–80.

    Article  PubMed  CAS  Google Scholar 

  182. Fournier, A. E., Nakamura, F., Kawamoto, S., Goshima, Y., Kalb, R. G., and Strittmatter, S. M. (2000) Semaphorin3A enhances endocytosis at sites of receptor-F-actin colocalization during growth cone collapse, J Cell Biol 149, 411–422.

    Article  PubMed  CAS  Google Scholar 

  183. Fan, J., Mansfield, S. G., Redmond, T., Gordon-Weeks, P. R., and Raper, J. A. (1993) The organization of F-actin and microtubules in growth cones exposed to a brain-derived collapsing factor, J Cell Biol 121, 867–878.

    Article  PubMed  CAS  Google Scholar 

  184. Serini, G., Valdembri, D., Zanivan, S., Morterra, G., Burkhardt, C., Caccavari, F., Zammataro, L., Primo, L., Tamagnone, L., Logan, M., Tessier-Lavigne, M., Taniguchi, M., Puschel, A. W., and Bussolino, F. (2003) Class 3 semaphorins control vascular morphogenesis by inhibiting integrin function, Nature 424, 391–397.

    Article  PubMed  CAS  Google Scholar 

  185. Kashiwagi, H., Shiraga, M., Kato, H., Kamae, T., Yamamoto, N., Tadokoro, S., Kurata, Y., Tomiyama, Y., and Kanakura, Y. (2005) Negative regulation of platelet function by a secreted cell repulsive protein, semaphorin 3A, Blood 106, 913–921.

    Article  PubMed  CAS  Google Scholar 

  186. Nasdala, I., Wolburg-Buchholz, K., Wolburg, H., Kuhn, A., Ebnet, K., Brachtendorf, G., Samulowitz, U., Kuster, B., Engelhardt, B., Vestweber, D., and Butz, S. (2002) A ­transmembrane tight junction protein ­selectively expressed on endothelial cells and platelets, Journal of Biological Chemistry 277, 16294–16303.

    Article  PubMed  CAS  Google Scholar 

  187. Sobocka, M. B., Sobocki, T., Banerjee, P., Weiss, C., Rushbrook, J. I., Norin, A. J., Hartwig, J., Salifu, M. O., Markell, M. S., Babinska, A., Ehrlich, Y. H., and Kornecki, E. (2000) Cloning of the human platelet F11 receptor: a cell adhesion molecule member of the immunoglobulin superfamily involved in platelet aggregation, Blood 95, 2600–2609.

    PubMed  CAS  Google Scholar 

  188. Hirata, K., Ishida, T., Penta, K., Rezaee, M., Yang, E., Wohlgemuth, J., and Quertermous, T. (2001) Cloning of an immunoglobulin family adhesion molecule selectively expressed by endothelial cells, Journal of Biological Chemistry 276, 16223–16231.

    Article  CAS  Google Scholar 

  189. Wegmann, F., Petri, B., Khandoga, A. G., Moser, C., Khandoga, A., Volkery, S., Li, H., Nasdala, I., Brandau, O., Fassler, R., Butz, S., Krombach, F., and Vestweber, D. (2006) ESAM supports neutrophil extravasation, activation of Rho, and VEGF-induced vascular permeability, Journal of Experimental Medicine 203, 1671–1677.

    Article  PubMed  CAS  Google Scholar 

  190. Stalker, T. J., Wu, J., Morgans, A., Traxler, E. A., Wang, L., Chatterjee, M. S., Lee, D., Quertermous, T., Hall, R. A., Hammer, D. A., Diamond, S. L., and Brass, L. F. (2009) Endothelial cell specific adhesion molecule (ESAM) localizes to platelet-platelet contacts and regulates thrombus formation in vivo, Journal of Thrombosis and Haemostasis 7, 1886–1896.

    Article  PubMed  CAS  Google Scholar 

  191. Naik, M. U., Stalker, T. J., Brass, L. F., and Naik, U. P. (2008) Junctional Adhesion Molecule a Helps Maintain Integrin alpha IIb beta 3 in Resting State, Blood 112, 48–48.

    Google Scholar 

  192. Naik, M. U., Stalker, T. J., Brass, L. F., and Naik, U. P. (2009) Platelet Junctional Adhesion Molecule-A Regulates Thrombosis by Negatively Regulating Outside-in Signaling through Integrin alpha IIb beta 3, Blood 114, 69–70.

    Article  Google Scholar 

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Authors and Affiliations

  1. Institute for Cardiovascular and Metabolic Research, School of Biological Sciences, The University of Reading, Reading, UK

    Chris I. Jones, Natasha E. Barrett, Leonardo A. Moraes & Jonathan M. Gibbins

  2. Health Innovations Research Institute, School of Medical Sciences, RMIT University, Bundoora, VIC, Australia

    Denise E. Jackson

Authors
  1. Chris I. Jones
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  2. Natasha E. Barrett
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  3. Leonardo A. Moraes
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  4. Jonathan M. Gibbins
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  5. Denise E. Jackson
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Correspondence to Jonathan M. Gibbins .

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Editors and Affiliations

  1. School of Biological Sciences, Inst. Cardiovascular & Metabolic Res., University of Reading, Reading, RG6 6UB, Berkshire, United Kingdom

    Jonathan M. Gibbins

  2. , Dept. Cell Physiology & Pharmacology, University of Leicester, University Road, Leicester, LE1 9HN, United Kingdom

    Martyn P. Mahaut-Smith

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Jones, C.I., Barrett, N.E., Moraes, L.A., Gibbins, J.M., Jackson, D.E. (2012). Endogenous Inhibitory Mechanisms and the Regulation of Platelet Function. In: Gibbins, J., Mahaut-Smith, M. (eds) Platelets and Megakaryocytes. Methods in Molecular Biology, vol 788. Springer, New York, NY. https://doi.org/10.1007/978-1-61779-307-3_23

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  • DOI: https://doi.org/10.1007/978-1-61779-307-3_23

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