Table of Contents
Journal of Signal Transduction
Volume 2012, Article ID 412089, 9 pages
http://dx.doi.org/10.1155/2012/412089
Review Article

The Small GTPase Rap1b: A Bidirectional Regulator of Platelet Adhesion Receptors

Department of Biology and Biotechnology, Division of Biochemistry, University of Pavia, Via Bassi 21, 27100 Pavia, Italy

Received 23 February 2012; Revised 12 April 2012; Accepted 27 April 2012

Academic Editor: Kris DeMali

Copyright © 2012 Gianni Francesco Guidetti and Mauro Torti. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Linked References

  1. R. W. Farndale, P. R. M. Siljander, D. J. Onley, P. Sundaresan, C. G. Knight, and M. J. Barnes, “Collagen-platelet interactions: recognition and signalling,” Biochemical Society Symposium, no. 70, pp. 81–94, 2003. View at Google Scholar · View at Scopus
  2. K. Broos, H. B. Feys, S. F. De Meyer, K. Vanhoorelbeke, and H. Deckmyn, “Platelets at work in primary hemostasis,” Blood Reviews, vol. 25, no. 4, pp. 155–167, 2011. View at Publisher · View at Google Scholar · View at Scopus
  3. S. Carrasco and I. Mérida, “Diacylglycerol, when simplicity becomes complex,” Trends in Biochemical Sciences, vol. 32, no. 1, pp. 27–36, 2007. View at Publisher · View at Google Scholar · View at Scopus
  4. Z. Li, M. K. Delaney, K. A. O'Brien, and X. Du, “Signaling during platelet adhesion and activation,” Arteriosclerosis, Thrombosis, and Vascular Biology, vol. 30, no. 12, pp. 2341–2349, 2010. View at Google Scholar
  5. D. S. Woulfe, “Platelet G protein-coupled receptors in hemostasis and thrombosis,” Journal of Thrombosis and Haemostasis, vol. 3, no. 10, pp. 2193–2200, 2005. View at Publisher · View at Google Scholar · View at Scopus
  6. F. J. T. Zwartkruis and J. L. Bos, “Ras and Rap1: two highly related small GTPases with distinct function,” Experimental Cell Research, vol. 253, no. 1, pp. 157–165, 1999. View at Publisher · View at Google Scholar · View at Scopus
  7. E. G. Lapetina, J. Carlos Lacal, B. R. Reep, and L. Molina y Vedia, “A ras-related protein is phosphorylated and translocated by agonists that increase cAMP levels in human platelets,” Proceedings of the National Academy of Sciences of the United States of America, vol. 86, no. 9, pp. 3131–3134, 1989. View at Google Scholar · View at Scopus
  8. T. E. White, J. C. Lacal, B. Reep, T. H. Fischer, E. G. Lapetina, and G. C. White, “Thrombolamban, the 22-kDa platelet substrate of cyclic AMP-dependent protein kinase, is immunologically homologous with the Ras family of GTP-binding proteins,” Proceedings of the National Academy of Sciences of the United States of America, vol. 87, no. 2, pp. 758–762, 1990. View at Google Scholar · View at Scopus
  9. P. G. Polakis, R. F. Weber, B. Nevins, J. R. Didsbury, T. Evans, and R. Snyderman, “Identification of the ral and rac1 gene products, low molecular mass GTP-binding proteins from human platelets,” The Journal of Biological Chemistry, vol. 264, no. 28, pp. 16383–16389, 1989. View at Google Scholar · View at Scopus
  10. Y. Nemoto, T. Namba, T. Teru-uchi, F. Ushikubi, N. Morii, and S. Narumiya, “A rho gene product in human blood platelets. I. Identification of the platelet substrate for botulinum C3 ADP-ribosyltransferase as rhoA protein,” The Journal of Biological Chemistry, vol. 267, no. 29, pp. 20916–20920, 1992. View at Google Scholar · View at Scopus
  11. P. G. Polakis, R. Snyderman, and T. Evans, “Characterization of G25K, a GTP-binding protein containing a novel putative nucleotide binding domain,” Biochemical and Biophysical Research Communications, vol. 160, no. 1, pp. 25–32, 1989. View at Google Scholar · View at Scopus
  12. M. Torti and E. G. Lapetina, “Structure and function of rap proteins in human platelets,” Thrombosis and Haemostasis, vol. 71, no. 5, pp. 533–543, 1994. View at Google Scholar · View at Scopus
  13. E. Caron, “Cellular functions of the Rap1 GTP-binding protein: a pattern emerges,” Journal of Cell Science, vol. 116, pp. 435–440, 2003. View at Publisher · View at Google Scholar · View at Scopus
  14. G. M. Bokoch, “Biology of the Rap proteins, members of the ras superfamily of GTP-binding proteins,” Biochemical Journal, vol. 289, pp. 17–24, 1993. View at Google Scholar · View at Scopus
  15. Y. Takai, T. Sasaki, and T. Matozaki, “Small GTP-binding proteins,” Physiological Reviews, vol. 81, no. 1, pp. 153–208, 2001. View at Google Scholar · View at Scopus
  16. S. Paganini, G. F. Guidetti, S. Catricalà et al., “Identification and biochemical characterization of Rap2C, a new member of the Rap family of small GTP-binding proteins,” Biochimie, vol. 88, no. 3-4, pp. 285–295, 2006. View at Publisher · View at Google Scholar · View at Scopus
  17. Z. Fu, S. H. Lee, A. Simonetta, J. Hansen, M. Sheng, and D. T. S. Pak, “Differential roles of Rap1 and Rap2 small GTPases in neurite retraction and synapse elimination in hippocampal spiny neurons,” Journal of Neurochemistry, vol. 100, no. 1, pp. 118–131, 2007. View at Publisher · View at Google Scholar · View at Scopus
  18. R. L. Stornetta and J. J. Zhu, “Ras and Rap signaling in synaptic plasticity and mental disorders,” Neuroscientist, vol. 17, no. 1, pp. 54–78, 2011. View at Publisher · View at Google Scholar · View at Scopus
  19. I. Canobbio, P. Trionfini, G. F. Guidetti, C. Balduini, and M. Torti, “Targeting of the small GTPase Rap2b, but not Rap1b, to lipid rafts is promoted by palmitoylation at Cys176 and Cys177 and is required for efficient protein activation in human platelets,” Cellular Signalling, vol. 20, no. 9, pp. 1662–1670, 2008. View at Publisher · View at Google Scholar · View at Scopus
  20. F. J. Klinz, R. Seifert, I. Schwaner, H. Gausepohl, R. Frank, and G. Schultz, “Generation of specific antibodies against the rap1A, rap1B and rap2 small GTP-binding proteins. Analysis of rap and ras proteins in membranes frome mammalian cells,” European Journal of Biochemistry, vol. 207, no. 1, pp. 207–213, 1992. View at Publisher · View at Google Scholar · View at Scopus
  21. M. Torti, G. Ramaschi, F. Sinigaglia, E. G. Lapetina, and C. Balduini, “Association of the low molecular weight GTP-binding protein rap2B with the cytoskeleton during platelet aggregation,” Proceedings of the National Academy of Sciences of the United States of America, vol. 90, no. 16, pp. 7553–7557, 1993. View at Google Scholar · View at Scopus
  22. M. Torti, G. Ramaschi, F. Sinigaglia, E. G. Lapetina, and C. Balduini, “Glycoprotein IIb-IIIa and the translocation of Rap2B to the platelet cytoskeleton,” Proceedings of the National Academy of Sciences of the United States of America, vol. 91, no. 10, pp. 4239–4243, 1994. View at Google Scholar · View at Scopus
  23. M. Torti, A. Bertoni, I. Canobbio, F. Sinigaglia, E. G. Lapetina, and C. Balduini, “Rap1B and Rap2B translocation to the cytoskeleton by von Willebrand factor involves FCγII receptor-mediated protein tyrosine phosphorylation,” The Journal of Biological Chemistry, vol. 274, no. 19, pp. 13690–13697, 1999. View at Publisher · View at Google Scholar · View at Scopus
  24. F. Greco, F. Sinigaglia, C. Balduini, and M. Torti, “Activation of the small GTPase Rap2B in agonist-stimulated human platelets,” Journal of Thrombosis and Haemostasis, vol. 2, no. 12, pp. 2223–2230, 2004. View at Publisher · View at Google Scholar · View at Scopus
  25. K. Eto, R. Murphy, S. W. Kerrigan et al., “Megakaryocytes derived from embryonic stem cells implicate CalDAG-GEFI in integrin signaling,” Proceedings of the National Academy of Sciences of the United States of America, vol. 99, no. 20, pp. 12819–12824, 2002. View at Publisher · View at Google Scholar · View at Scopus
  26. J. R. Crittenden, W. Bergmeier, Y. Zhang et al., “CalDAG-GEFI integrates signaling for platelet aggregation and thrombus formation,” Nature Medicine, vol. 10, no. 9, pp. 982–986, 2004. View at Publisher · View at Google Scholar · View at Scopus
  27. B. Bernardi, G. F. Guidetti, F. Campus et al., “The small GTPase Rap1b regulates the cross talk between platelet integrin α2β1 and integrin αIIbβ 3,” Blood, vol. 107, no. 7, pp. 2728–2735, 2006. View at Publisher · View at Google Scholar · View at Scopus
  28. L. Stefanini, R. C. Roden, and W. Bergmeier, “CalDAG-GEFI is at the nexus of calcium-dependent platelet activation,” Blood, vol. 114, no. 12, pp. 2506–2514, 2009. View at Publisher · View at Google Scholar · View at Scopus
  29. J. Schultess, O. Danielewski, and A. P. Smolenski, “Rap1GAP2 is a new GTPase-activating protein of Rap1 expressed in human platelets,” Blood, vol. 105, no. 8, pp. 3185–3192, 2005. View at Publisher · View at Google Scholar · View at Scopus
  30. M. J. Lorenowicz, J. van Gils, M. de Boer, P. L. Hordijk, and M. Fernandez-Borja, “Epac1-Rap1 signaling regulates monocyte adhesion and chemotaxis,” Journal of Leukocyte Biology, vol. 80, no. 6, pp. 1542–1552, 2006. View at Publisher · View at Google Scholar · View at Scopus
  31. M. Hoffmeister, P. Riha, O. Neumüller, O. Danielewski, J. Schultess, and A. P. Smolenski, “Cyclic nucleotide-dependent protein kinases inhibit binding of 14-3-3 to the GTPase-activating protein Rap1GAP2 in platelets,” The Journal of Biological Chemistry, vol. 283, no. 4, pp. 2297–2306, 2008. View at Publisher · View at Google Scholar · View at Scopus
  32. K. A. Reedquist, E. Ross, E. A. Koop et al., “The small GTPase, Rap1, mediates CD31-induced integrin adhesion,” Journal of Cell Biology, vol. 148, no. 6, pp. 1151–1158, 2000. View at Publisher · View at Google Scholar · View at Scopus
  33. E. Caron, A. J. Self, and A. Hall, “The GTPase rap1 controls functional activation of macrophage integrin αMβ2 by LPS and other inflammatory mediators,” Current Biology, vol. 10, no. 16, pp. 974–978, 2000. View at Publisher · View at Google Scholar · View at Scopus
  34. K. Katagiri, M. Hattori, N. Minato, S. K. Irie, K. Takatsu, and T. Kinashi, “Rap1 is a potent activation signal for leukocyte function-associated antigen 1 distinct from protein kinase C and phosphatidylinositol-3-OH kinase,” Molecular and Cellular Biology, vol. 20, no. 6, pp. 1956–1969, 2000. View at Publisher · View at Google Scholar · View at Scopus
  35. J. M. Enserink, L. S. Price, T. Methi et al., “The cAMP-Epac-Rap1 pathway regulates cell spreading and cell adhesion to laminin-5 through, the α3β1 integrin but not the α6β4 integrin,” The Journal of Biological Chemistry, vol. 279, no. 43, pp. 44889–44896, 2004. View at Publisher · View at Google Scholar · View at Scopus
  36. R. J. Faull and M. H. Ginsberg, “Inside-out signaling through integrins,” Journal of the American Society of Nephrology, vol. 7, no. 8, pp. 1091–1097, 1996. View at Google Scholar · View at Scopus
  37. M. Chrzanowska-Wodnicka, S. S. Smyth, S. M. Schoenwaelder, T. H. Fischer, and G. C. White, “Rap1b is required for normal platelet function and hemostasis in mice,” Journal of Clinical Investigation, vol. 115, no. 3, pp. 680–687, 2005. View at Publisher · View at Google Scholar · View at Scopus
  38. M. Stolla, L. Stefanini, R. C. Roden et al., “The kinetics of αIIbβ3 activation determines the size and stability of thrombi in mice: Implications for antiplatelet therapy,” Blood, vol. 117, no. 3, pp. 1005–1013, 2011. View at Publisher · View at Google Scholar · View at Scopus
  39. S. Grüner, M. Prostredna, V. Schulte et al., “Multiple integrin-ligand interactions synergize in shear-resistant platelet adhesion at sites of arterial injury in vivo,” Blood, vol. 102, no. 12, pp. 4021–4027, 2003. View at Publisher · View at Google Scholar · View at Scopus
  40. A. Bertoni, S. Tadokoro, K. Eto et al., “Relationships between Rap1b, affinity modulation of integrin αIIbβ3 and the actin cytoskeleton,” The Journal of Biological Chemistry, vol. 277, no. 28, pp. 25715–25721, 2002. View at Publisher · View at Google Scholar · View at Scopus
  41. D. A. Calderwood, R. Zent, R. Grant, D. J. G. Rees, R. O. Hynes, and M. H. Ginsberg, “The talin head domain binds to integrin β subunit cytoplasmic tails and regulates integrin activation,” The Journal of Biological Chemistry, vol. 274, no. 40, pp. 28071–28074, 1999. View at Publisher · View at Google Scholar · View at Scopus
  42. S. Tadokoro, S. J. Shattil, K. Eto et al., “Talin binding to integrin β tails: a final common step in integrin activation,” Science, vol. 302, no. 5642, pp. 103–106, 2003. View at Publisher · View at Google Scholar · View at Scopus
  43. D. S. Harburger, M. Bouaouina, and D. A. Calderwood, “Kindlin-1 and -2 directly bind the C-terminal region of β integrin cytoplasmic tails and exert integrin-specific activation effects,” The Journal of Biological Chemistry, vol. 284, no. 17, pp. 11485–11497, 2009. View at Publisher · View at Google Scholar · View at Scopus
  44. J. Han, C. J. Lim, N. Watanabe et al., “Reconstructing and deconstructing agonist-induced activation of integrin alphaIIbbeta3,” Current Biology, vol. 16, no. 18, pp. 1796–1806, 2006. View at Google Scholar
  45. E. M. Lafuente, A. A. F. L. van Puijenbroek, M. Krause et al., “RIAM, an Ena/VASP and profilin ligand, interacts with Rap1-GTP and mediates Rap1-induced adhesion,” Developmental Cell, vol. 7, no. 4, pp. 585–595, 2004. View at Publisher · View at Google Scholar · View at Scopus
  46. N. Watanabe, L. Bodin, M. Pandey et al., “Mechanisms and consequences of agonist-induced talin recruitment to platelet integrin αIIbβ3,” Journal of Cell Biology, vol. 181, no. 7, pp. 1211–1222, 2008. View at Publisher · View at Google Scholar · View at Scopus
  47. S. M. Cifuni, D. D. Wagner, and W. Bergmeier, “CalDAG-GEFI and protein kinase C represent alternative pathways leading to activation of integrin αIIbβ3 in platelets,” Blood, vol. 112, no. 5, pp. 1696–1703, 2008. View at Publisher · View at Google Scholar · View at Scopus
  48. S. M. Jung and M. Moroi, “Platelets interact with soluble and insoluble collagens through characteristically different reactions,” The Journal of Biological Chemistry, vol. 273, no. 24, pp. 14827–14837, 1998. View at Publisher · View at Google Scholar · View at Scopus
  49. O. Inoue, K. Suzuki-Inoue, W. L. Dean, J. Frampton, and S. P. Watson, “Integrin α2β1 mediates outside-in regulation of platelet spreading on collagen through activation of Src kinases and PLCγ2,” Journal of Cell Biology, vol. 160, no. 5, pp. 769–780, 2003. View at Publisher · View at Google Scholar · View at Scopus
  50. H. Chen and M. L. Kahn, “Reciprocal signaling by integrin and nonintegrin receptors during collagen activation of platelets,” Molecular and Cellular Biology, vol. 23, no. 14, pp. 4764–4777, 2003. View at Publisher · View at Google Scholar · View at Scopus
  51. Z. Wang, S. P. Holly, M. K. Larson et al., “Rap1b is critical for glycoprotein VI-mediated but not ADP receptor-mediated α2β1 activation,” Journal of Thrombosis and Haemostasis, vol. 7, no. 4, pp. 693–700, 2009. View at Publisher · View at Google Scholar · View at Scopus
  52. W. Bergmeier, T. Goerge, H. W. Wang et al., “Mice lacking the signaling molecule CalDAG-GEFI represent a model for leukocyte adhesion deficiency type III,” Journal of Clinical Investigation, vol. 117, no. 6, pp. 1699–1707, 2007. View at Publisher · View at Google Scholar · View at Scopus
  53. L. Stefanini, Y. Boulaftali, T. D. Ouellette et al., “Rap1-Rac1 circuits potentiate platelet activation,” Arteriosclerosis, Thrombosis, and Vascular Biology, vol. 32, no. 2, pp. 434–441, 2012. View at Google Scholar
  54. H. K. Nieuwenhuis, J. W. N. Akkerman, W. P. M. Houdijk, and J. J. Sixma, “Human blood platelets showing no response to collagen fail to express surface glycoprotein Ia,” Nature, vol. 318, no. 6045, pp. 470–472, 1985. View at Google Scholar · View at Scopus
  55. B. Kehrel, “Platelet-collagen interactions,” Seminars in Thrombosis and Hemostasis, vol. 21, no. 2, pp. 123–129, 1995. View at Google Scholar
  56. J. Emsley, C. G. Knight, R. W. Farndale, M. J. Barnes, and R. C. Liddington, “Structural basis of collagen recognition by integrin α2β1,” Cell, vol. 101, no. 1, pp. 47–56, 2000. View at Google Scholar · View at Scopus
  57. P. R. M. Siljander, S. Hamaia, A. R. Peachey et al., “Integrin activation state determines selectivity for novel recognition sites in fibrillar collagens,” The Journal of Biological Chemistry, vol. 279, no. 46, pp. 47763–47772, 2004. View at Publisher · View at Google Scholar · View at Scopus
  58. N. Raynal, S. W. Hamaia, P. R. M. Siljander et al., “Use of synthetic peptides to locate novel integrin α2β1-binding motifs in human collagen III,” The Journal of Biological Chemistry, vol. 281, no. 7, pp. 3821–3831, 2006. View at Publisher · View at Google Scholar · View at Scopus
  59. M. Schaff, N. Receveur, C. Bourdon et al., “Novel function of tenascin-C, a matrix protein relevant to atherosclerosis, in platelet recruitment and activation under flow,” Arteriosclerosis, Thrombosis, and Vascular Biology, vol. 31, no. 1, pp. 117–124, 2011. View at Publisher · View at Google Scholar · View at Scopus
  60. G. Guidetti, A. Bertoni, M. Viola, E. Tira, C. Balduini, and M. Torti, “The small proteoglycan decorin supports adhesion and activation of human platelets,” Blood, vol. 100, no. 5, pp. 1707–1714, 2002. View at Google Scholar · View at Scopus
  61. G. F. Guidetti, B. Bernardi, A. Consonni et al., “Integrin α2β1 induces phosphorylation-dependent and phosphorylation-independent activation of phospholipase Cγ2 in platelets: role of Src kinase and Rac GTPase,” Journal of Thrombosis and Haemostasis, vol. 7, no. 7, pp. 1200–1206, 2009. View at Publisher · View at Google Scholar · View at Scopus
  62. A. Consonni, L. Cipolla, G. Guidetti et al., “Role and regulation of phosphatidylinositol 3-kinase beta in platelet integrin alpha2beta1 signaling,” Blood, vol. 119, no. 3, pp. 847–856, 2012. View at Google Scholar
  63. D. Woulfe, H. Jiang, R. Mortensen, J. Yang, and L. F. Brass, “Activation of Rap1B by Gi family members in platelets,” The Journal of Biological Chemistry, vol. 277, no. 26, pp. 23382–23390, 2002. View at Publisher · View at Google Scholar · View at Scopus
  64. P. Lova, S. Paganini, E. Hirsch et al., “A selective role for phosphatidylinositol 3,4,5-trisphosphate in the Gi-dependent activation of platelet Rap1B,” The Journal of Biological Chemistry, vol. 278, no. 1, pp. 131–138, 2003. View at Publisher · View at Google Scholar · View at Scopus
  65. I. Canobbio, L. Stefanini, L. Cipolla et al., “Genetic evidence for a predominant role of PI3Kβ catalytic activity in ITAM- and integrin-mediated signaling in platelets,” Blood, vol. 114, no. 10, pp. 2193–2196, 2009. View at Publisher · View at Google Scholar · View at Scopus
  66. O. Berlanga, R. Bobe, M. Becker et al., “Expression of the collagen receptor glycoprotein VI during megakaryocyte differentiation,” Blood, vol. 96, no. 8, pp. 2740–2745, 2000. View at Google Scholar · View at Scopus
  67. B. Nieswandt, W. Bergmeier, V. Schulte, K. Rackebrandt, J. E. Gessner, and H. Zirngibl, “Expression and function of the mouse collagen receptor glycoprotein VI is strictly dependent on its association with the FcRγ chain,” The Journal of Biological Chemistry, vol. 275, no. 31, pp. 23998–24002, 2000. View at Publisher · View at Google Scholar · View at Scopus
  68. K. L. Sarratt, H. Chen, M. M. Zutter, S. A. Santoro, D. A. Hammer, and M. L. Kahn, “GPVI and α2β1 play independent critical roles during platelet adhesion and aggregate formation to collagen under flow,” Blood, vol. 106, no. 4, pp. 1268–1277, 2005. View at Publisher · View at Google Scholar · View at Scopus
  69. S. P. Watson, J. M. Auger, O. J. T. McCarty, and A. C. Pearce, “GPVI and integrin αIIbβ3 signaling in platelets,” Journal of Thrombosis and Haemostasis, vol. 3, no. 8, pp. 1752–1762, 2005. View at Publisher · View at Google Scholar · View at Scopus
  70. T. Ichinohe, H. Takayama, Y. Ezumi et al., “Collagen-stimulated activation of Syk but not c-Src is severely compromised in human platelets lacking membrane glycoprotein VI,” The Journal of Biological Chemistry, vol. 272, no. 1, pp. 63–68, 1997. View at Publisher · View at Google Scholar · View at Scopus
  71. K. Kato, T. Kanaji, S. Russell et al., “The contribution of glycoprotein VI to stable platelet adhesion and thrombus formation illustrated by targeted gene deletion,” Blood, vol. 102, no. 5, pp. 1701–1707, 2003. View at Publisher · View at Google Scholar · View at Scopus
  72. M. Moroi, S. M. Jung, M. Okuma, and K. Shinmyozu, “A patient with platelets deficient in glycoprotein VI that lack both collagen-induced aggregation and adhesion,” Journal of Clinical Investigation, vol. 84, no. 5, pp. 1440–1445, 1989. View at Google Scholar · View at Scopus
  73. H. Kojima, M. Moroi, S. M. Jung et al., “Characterization of a patient with glycoprotein (GP) VI deficiency possessing neither anti-GPVI autoantibody nor genetic aberration,” Journal of Thrombosis and Haemostasis, vol. 4, no. 11, pp. 2433–2442, 2006. View at Publisher · View at Google Scholar · View at Scopus
  74. B. Nieswandt, V. Schulte, W. Bergmeier et al., “Long-term antithrombotic protection by in vivo depletion of platelet glycoprotein VI in mice,” Journal of Experimental Medicine, vol. 193, no. 4, pp. 459–469, 2001. View at Publisher · View at Google Scholar · View at Scopus
  75. T. Nakamura, J. I. Kambayashi, M. Okuma, and N. N. Tandon, “Activation of the GP IIb-IIIa complex induced by platelet adhesion to collagen is mediated by both α2β1 integrin and GP VI,” The Journal of Biological Chemistry, vol. 274, no. 17, pp. 11897–11903, 1999. View at Publisher · View at Google Scholar · View at Scopus
  76. T. M. Quinton, F. Ozdener, C. Dangelmaier, J. L. Daniel, and S. P. Kunapuli, “Glycoprotein VI-mediated platelet fibrinogen receptor activation occurs through calcium-sensitive and PKC-sensitive pathways without a requirement for secreted ADP,” Blood, vol. 99, no. 9, pp. 3228–3234, 2002. View at Publisher · View at Google Scholar · View at Scopus
  77. M. K. Larson, H. Chen, M. L. Kahn et al., “Identification of P2Y12-dependent and -independent mechanisms of glycoprotein VI-mediated Rap1 activation in platelets,” Blood, vol. 101, no. 4, pp. 1409–1415, 2003. View at Publisher · View at Google Scholar · View at Scopus
  78. K. Gilio, I. C. A. Munnix, P. Mangin et al., “Non-redundant roles of phosphoinositide 3-kinase isoforms α and β in glycoprotein VI-induced platelet signaling and thrombus formation,” The Journal of Biological Chemistry, vol. 284, no. 49, pp. 33750–33762, 2009. View at Publisher · View at Google Scholar · View at Scopus
  79. G. Zhang, B. Xiang, and S. Ye, “Distinct roles for Rap1b protein in platelet secretion and integrin alphaIIbbeta3 outside-in signaling,” The Journal of Biological Chemistry, vol. 286, no. 45, pp. 39466–39477, 2011. View at Google Scholar
  80. Y. Ohba, N. Mochizuki, K. Matsuo et al., “Rap2 as a slowly responding molecular switch in the Rap1 signaling cascade,” Molecular and Cellular Biology, vol. 20, no. 16, pp. 6074–6083, 2000. View at Publisher · View at Google Scholar · View at Scopus
  81. B. Savage, E. Saldívar, and Z. M. Ruggeri, “Initiation of platelet adhesion by arrest onto fibrinogen or translocation on von Willebrand factor,” Cell, vol. 84, no. 2, pp. 289–297, 1996. View at Publisher · View at Google Scholar · View at Scopus
  82. P. Thiagarajan and K. L. Kelly, “Exposure of binding sites for vitronectin on platelets following stimulation,” The Journal of Biological Chemistry, vol. 263, no. 6, pp. 3035–3038, 1988. View at Google Scholar · View at Scopus
  83. M. H. Ginsberg, J. Forsyth, and A. Lightsey, “Reduced surface expression and binding of fibronectin by thrombin-stimulated thrombasthenic platelets,” Journal of Clinical Investigation, vol. 71, no. 3, pp. 619–624, 1983. View at Google Scholar · View at Scopus
  84. J. Karczewski, K. A. Knudsen, L. Smith, A. Murphy, V. L. Rothman, and G. P. Tuszynski, “The interaction of thrombospondin with platelet glycoprotein GPIIb-IIIa,” The Journal of Biological Chemistry, vol. 264, no. 35, pp. 21322–21326, 1989. View at Google Scholar · View at Scopus
  85. Z. M. Ruggeri, “Mechanisms initiating platelet thrombus formation,” Thrombosis and Haemostasis, vol. 78, no. 1, pp. 611–616, 1997. View at Google Scholar · View at Scopus
  86. H. J. Weiss, V. T. Turitto, and H. R. Baumgartner, “Further evidence that glycoprotein IIb-IIIa mediates platelet spreading on subendothelium,” Thrombosis and Haemostasis, vol. 65, no. 2, pp. 202–205, 1991. View at Google Scholar · View at Scopus
  87. S. J. Shattil and P. J. Newman, “Integrins: dynamic scaffolds for adhesion and signaling in platelets,” Blood, vol. 104, no. 6, pp. 1606–1615, 2004. View at Publisher · View at Google Scholar · View at Scopus
  88. S. M. Schoenwaelder, Y. Yuan, P. Cooray, H. H. Salem, and S. P. Jackson, “Calpain cleavage of focal adhesion proteins regulates the cytoskeletal attachment of integrin α(IIb)β3 (platelet glycoprotein IIb/IIIa) and the cellular retraction of fibrin clots,” The Journal of Biological Chemistry, vol. 272, no. 3, pp. 1694–1702, 1997. View at Publisher · View at Google Scholar · View at Scopus
  89. M. J. VanWijk, E. VanBavel, A. Sturk, and R. Nieuwland, “Microparticles in cardiovascular diseases,” Cardiovascular Research, vol. 59, no. 2, pp. 277–287, 2003. View at Publisher · View at Google Scholar · View at Scopus
  90. C. P. Chang, J. Zhao, T. Wiedmer, and P. J. Sims, “Contribution of platelet microparticle formation and granule secretion to the transmembrane migration of phosphatidylserine,” The Journal of Biological Chemistry, vol. 268, no. 10, pp. 7171–7178, 1993. View at Google Scholar · View at Scopus
  91. B. Savage, F. Almus-Jacobs, and Z. M. Ruggeri, “Specific synergy of multiple substrate-receptor interactions in platelet thrombus formation under flow,” Cell, vol. 94, no. 5, pp. 657–666, 1998. View at Publisher · View at Google Scholar · View at Scopus
  92. Y. Wu, K. Suzuki-Inoue, K. Satoh et al., “Role of Fc receptor γ-chain in platelet glycoprotein Ib-mediated signaling,” Blood, vol. 97, no. 12, pp. 3836–3845, 2001. View at Publisher · View at Google Scholar · View at Scopus
  93. A. Kasirer-Friede, M. R. Cozzi, M. Mazzucato, L. De Marco, Z. M. Ruggeri, and S. J. Shattil, “Signaling through GP Ib-IX-V activates αIIbβ3 independently of other receptors,” Blood, vol. 103, no. 9, pp. 3403–3411, 2004. View at Publisher · View at Google Scholar · View at Scopus
  94. P. Lova, S. Paganini, F. Sinigaglia, C. Balduini, and M. Torti, “A Gi-dependent pathway is required for activation of the small GTPase Rap1B in human platelets,” The Journal of Biological Chemistry, vol. 277, no. 14, pp. 12009–12015, 2002. View at Publisher · View at Google Scholar · View at Scopus