Targeting platelet inhibition receptors for novel therapies: PECAM-1 and G6b-B

References

• Vivier E, Daeron M. Immunoreceptor tyrosine-based inhibition motifs. Immunol Today 1997;186:p.286–91. DOI:https://doi.org/10.1016/S0167-5699(97)80025-4
   PubMedGoogle Scholar
• Burshtyn DN, Yang W, Yi T, Long EO. A novel phosphotyrosine motif with a critical amino acid at position −2 for the SH2 domain-mediated activation of the tyrosine phosphatase SHP-1. J Biol Chem 1997;27220:p.13066–13072. DOI:https://doi.org/10.1074/jbc.272.20.13066
   PubMed Web of Science ®Google Scholar
• Daeron M. Intracytoplasmic sequences involved in the biological properties of low-affinity receptors for IgG expressed by murine macrophages. Braz J Med Biol Res 1995;283:p. 263–74.
   PubMed Web of Science ®Google Scholar
• D’Ambrosio D, Hippen K, Minskoff S, Mellman I, Pani G, Siminovitch K, Cambier J. Recruitment and activation of PTP1C in negative regulation of antigen receptor signaling by Fc gamma RIIB1. Science 1995;2685208:p.293–297. DOI:https://doi.org/10.1126/science.7716523
   PubMed Web of Science ®Google Scholar
• Reth M. Antigen receptor tail clue. Nature 1989;3386214:p.383–384. DOI:https://doi.org/10.1038/338383b0
   PubMed Web of Science ®Google Scholar
• Cambier JC. New nomenclature for the Reth motif (or ARH1/TAM/ARAM/YXXL). Immunol Today 1995;162:p.110. DOI:https://doi.org/10.1016/0167-5699(95)80105-7
   PubMedGoogle Scholar
• Hughes CE, Sinha U, Pandey A, Eble JA, O’Callaghan CA, Watson SP. Critical Role for an acidic amino acid region in platelet signaling by the HemITAM (hemi-immunoreceptor tyrosine-based activation motif) containing receptor CLEC-2 (C-type lectin receptor-2). J Biol Chem 2013;2887:p. 5127–35. DOI:https://doi.org/10.1074/jbc.M112.411462
   PubMed Web of Science ®Google Scholar
• Amigorena S, Bonnerot C, Drake JR, Choquet D, Hunziker W, Guillet JG, Webster P, Sautes C, Mellman I, Fridman WH. Cytoplasmic domain heterogeneity and functions of IgG Fc receptors in B lymphocytes. Science 1992;2565065:p. 1808–12. DOI:https://doi.org/10.1126/science.1535455
   PubMed Web of Science ®Google Scholar
• Muta T, Kurosaki T, Misulovin Z, Sanchez M, Nussenzweig MC, Ravetch JV. A 13-amino-acid motif in the cytoplasmic domain of Fc gamma RIIB modulates B-cell receptor signalling. Nature 1994;3696478:p. 340. https://doi.org/10.1038/369340a0
   PubMed Web of Science ®Google Scholar
• Daeron M, Latour S, Malbec O, Espinosa E, Pina P, Pasmans S, Fridman WH. The same tyrosine-based inhibition motif, in the intracytoplasmic domain of Fc gamma RIIB, regulates negatively BCR-, TCR-, and FcR-dependent cell activation. Immunity 1995;35:p. 635–46. https://doi.org/10.1016/1074-7613(95)90134-5
   PubMed Web of Science ®Google Scholar
• Newman PJ. Switched at birth: a new family for PECAM-1. J Clin Invest 1999;1031:p. 5–9. DOI:https://doi.org/10.1172/JCI5928
   PubMed Web of Science ®Google Scholar
• Coxon CH, Geer MJ, Senis YA. ITIM receptors: more than just inhibitors of platelet activation. Blood 2017;12926:p. 3407–3418. DOI:https://doi.org/10.1182/blood-2016-12-720185
   PubMed Web of Science ®Google Scholar
• Sidorenko SP, Clark EA. The dual-function CD150 receptor subfamily: the viral attraction. Nat Immunol 2003;41:p. 19–24. https://doi.org/10.1038/ni0103-19
   PubMed Web of Science ®Google Scholar
• Gibbins JM. The negative regulation of platelet function: extending the role of the ITIM. Trends Cardiovasc Med 2002;125:p. 213–9. https://doi.org/10.1016/S1050-1738(02)00164-0
   PubMed Web of Science ®Google Scholar
• Washington AV, Schubert RL, Quigley L, Disipio T, Feltz R, Cho EH, McVicar DW. A TREM family member, TLT-1, is found exclusively in the alpha-granules of megakaryocytes and platelets. Blood 2004;1044:p.1042–7. https://doi.org/10.1182/blood-2004-01-0315
   PubMed Web of Science ®Google Scholar
• Steevels TA, Westerlaken GHA, Tijssen MR, Coffer PJ, Lenting PJ, Akkerman JWN, Meyaard L. Co-expression of the collagen receptors leukocyte-associated immunoglobulin-like receptor-1 and glycoprotein VI on a subset of megakaryoblasts. Haematologica 2010;9512:p. 2005–12. https://doi.org/10.3324/haematol.2010.026120
   PubMed Web of Science ®Google Scholar
• Senis YA, Tomlinson MG, García Á, Dumon S, Heath VL, Herbert J, Cobbold SP, Spalton JC, Ayman S, Antrobus R, et al. 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. Mol Cell Proteomics 2007;63:p. 548–64. https://doi.org/10.1074/mcp.D600007-MCP200
   PubMed Web of Science ®Google Scholar
• Suzuki-Inoue K, Tulasne D, Shen Y, Bori-Sanz T, Inoue O, Jung SM, Moroi M, Andrews RK, Berndt MC, Watson SP, et al. Association of Fyn and Lyn with the proline-rich domain of glycoprotein VI regulates intracellular signaling. J Biol Chem 2002;27724:p. 21561–6. https://doi.org/10.1074/jbc.M201012200
   PubMed Web of Science ®Google Scholar
• Locke D, Chen H, Liu Y, Liu C, Kahn ML. Lipid rafts orchestrate signaling by the platelet receptor glycoprotein VI. J Biol Chem 2002:27721:p. 18801–9. https://doi.org/10.1074/jbc.M111520200
   PubMed Web of Science ®Google Scholar
• Wonerow P, OBERGFELL A, WILDE JI, BOBE R, ASAZUMA N, BRDIČKA T, LEO A, SCHRAVEN B, HOŘEJŠÍ V, SHATTIL SJ, et al. Differential role of glycolipid-enriched membrane domains in glycoprotein VI- and integrin-mediated phospholipase Cgamma2 regulation in platelets. Biochem J 2002:3643:p. 755–65. https://doi.org/10.1042/bj20020128
   PubMed Web of Science ®Google Scholar
• Pasquet JM, Gross B, Quek L, Asazuma N, Zhang W, Sommers CL, Schweighoffer E, Tybulewicz V, Judd B, Lee JR, et al. LAT is required for tyrosine phosphorylation of phospholipase cgamma2 and platelet activation by the collagen receptor GPVI. Mol Cell Biol 1999;1912:p. 8326–34. https://doi.org/10.1128/MCB.19.12.8326
   PubMed Web of Science ®Google Scholar
• Billadeau DD, Leibson PJ. ITAMs versus ITIMs: striking a balance during cell regulation. J Clin Invest 2002;1092:p. 161–8. https://doi.org/10.1172/JCI0214843
   PubMed Web of Science ®Google Scholar
• Moraes LA, Barrett NE, Jones CI, Holbrook LM, Spyridon M, Sage T, Newman DK, Gibbins JM.. Platelet endothelial cell adhesion molecule-1 regulates collagen-stimulated platelet function by modulating the association of phosphatidylinositol 3-kinase with Grb-2-associated binding protein-1 and linker for activation of T cells. J Thromb Haemost 2010;811:p. 2530–41. https://doi.org/10.1111/j.1538-7836.2010.04025.x
   PubMed Web of Science ®Google Scholar
• Wee JL, Jackson DE. The Ig-ITIM superfamily member PECAM-1 regulates the “outside-in” signaling properties of integrin alpha(IIb)beta3 in platelets. Blood 2005;10612:p. 3816–23. https://doi.org/10.1182/blood-2005-03-0911
   PubMed Web of Science ®Google Scholar
• Mazharian A, Mori J, Wang Y-J, Heising S, Neel BG, Watson SP, Senis YA. Megakaryocyte-specific deletion of the protein-tyrosine phosphatases Shp1 and Shp2 causes abnormal megakaryocyte development, platelet production, and function. Blood 2013;12120:p. 4205–20. https://doi.org/10.1182/blood-2012-08-449272
   PubMed Web of Science ®Google Scholar
• Yip J, Alshahrani M, Beauchemin N, Jackson DE. CEACAM1 regulates integrin alphaIIbbeta3-mediated functions in platelets. Platelets 2016;272:p. 168–77. https://doi.org/10.3109/09537104.2015.1064102
   PubMed Web of Science ®Google Scholar
• Alshahrani MM, Kyriacou RP, O’Malley CJ, Heinrich G, Najjar SM, Jackson DE. CEACAM2 positively regulates integrin alphaIIbbeta3-mediated platelet functions. Platelets 2016;278:p. 743–750. https://doi.org/10.3109/09537104.2016.1171834
   PubMed Web of Science ®Google Scholar
• Stefanini L, Bergmeier W. Negative regulators of platelet activation and adhesion. J Thromb Haemost 2018;162:p. 220–230. https://doi.org/10.1111/jth.13910
   PubMed Web of Science ®Google Scholar
• Newman PJ, Berndt M, Gorski J, White G, Lyman S, Paddock C, Muller W. PECAM-1 (CD31) cloning and relation to adhesion molecules of the immunoglobulin gene superfamily. Science 1990;2474947:p. 1219–22. https://doi.org/10.1126/science.1690453
   PubMed Web of Science ®Google Scholar
• Stockinger H, Gadd SJ, Eher R, Majdic O, Schreiber W, Kasinrerk W, Strass B, Schnabl E, Knapp W. Molecular characterization and functional analysis of the leukocyte surface protein CD31. J Immunol 1990;14511:p. 3889–97.
   PubMed Web of Science ®Google Scholar
• Albelda SM, Oliver PD, Romer LH, Buck CA. EndoCAM: a novel endothelial cell-cell adhesion molecule. J Cell Biol 1990;110(4):p. 1227–37. https://doi.org/10.1083/jcb.110.4.1227
   PubMed Web of Science ®Google Scholar
• Burkhart JM, Vaudel M, Gambaryan S, Radau S, Walter U, Martens L, Geiger J, Sickmann A, Zahedi RP. The first comprehensive and quantitative analysis of human platelet protein composition allows the comparative analysis of structural and functional pathways. Blood 2012;120(15):p. e73–82. https://doi.org/10.1182/blood-2012-04-416594
   PubMed Web of Science ®Google Scholar
• Zeiler M, Moser M, Mann M. Copy number analysis of the murine platelet proteome spanning the complete abundance range. Mol Cell Proteomics 2014;1312:p. 3435–45. https://doi.org/10.1074/mcp.M114.038513
   PubMed Web of Science ®Google Scholar
• Novinska M, Rathore V, Newman DK, Newman PJ. Chapter 11—Pecam-1 Platelets. 2007. Academic Press,Pages 221-230,ISBN 9780123693679, https://doi.org/10.1016/B978-012369367-9/50773-4.
   Google Scholar
• Jones CI, Garner SF, Moraes LA, Kaiser WJ, Rankin A, Ouwehand WH, Goodall AH, Gibbins JM. PECAM-1 expression and activity negatively regulate multiple platelet signaling pathways. FEBS Lett 2009;58322:p. 3618–24. https://doi.org/10.1016/j.febslet.2009.10.037
   PubMed Web of Science ®Google Scholar
• Patil S, Newman DK, Newman PJ. Platelet endothelial cell adhesion molecule-1 serves as an inhibitory receptor that modulates platelet responses to collagen. Blood 2001;976:p. 1727–32. https://doi.org/10.1182/blood.V97.6.1727
   PubMed Web of Science ®Google Scholar
• Falati S, Patil S, Gross PL, Stapleton M, Merrill-Skoloff G, Barrett NE, Pixton KL, Weiler H, Cooley B, Newman DK, et al. Platelet PECAM-1 inhibits thrombus formation in vivo. Blood 2006;1072:p. 535–41. https://doi.org/10.1182/blood-2005-04-1512
   PubMed Web of Science ®Google Scholar
• Kirschbaum NE, Gumina RJ, Newman PJ. Organization of the gene for human platelet/endothelial cell adhesion molecule-1 shows alternatively spliced isoforms and a functionally complex cytoplasmic domain. Blood 1994;8412:p. 4028–37. https://doi.org/10.1182/blood.V84.12.4028.bloodjournal84124028
   PubMed Web of Science ®Google Scholar
• Bergom C, Paddock C, Gao C, Holyst T, Newman DK, Newman PJ. An alternatively spliced isoform of PECAM-1 is expressed at high levels in human and murine tissues, and suggests a novel role for the C-terminus of PECAM-1 in cytoprotective signaling. J Cell Sci 2008;1218:p. 1235–42. https://doi.org/10.1242/jcs.025163
   PubMed Web of Science ®Google Scholar
• Newton JP, Hunter AP, Simmons DL, Buckley CD, Harvey DJ. CD31 (PECAM-1) exists as a dimer and is heavily N-glycosylated. Biochem Biophys Res Commun 1999;2612:283–291. https://doi.org/10.1006/bbrc.1999.1018
   PubMed Web of Science ®Google Scholar
• Newman PJ, Newman DK. Signal transduction pathways mediated by PECAM-1: new roles for an old molecule in platelet and vascular cell biology. Arterioscler Thromb Vasc Biol 2003;236:p. 953–64. https://doi.org/10.1161/01.ATV.0000071347.69358.D9
   PubMed Web of Science ®Google Scholar
• Jackson DE, Kupcho KR, Newman PJ. 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 1997;27240:p. 24868–75. https://doi.org/10.1074/jbc.272.40.24868
   PubMed Web of Science ®Google Scholar
• Paddock C, Lytle BL, Peterson FC, Holyst T, Newman PJ, Volkman BF, Newman DK. Residues within a lipid-associated segment of the PECAM-1 cytoplasmic domain are susceptible to inducible, sequential phosphorylation. Blood 2011;11722:p. 6012–23. https://doi.org/10.1182/blood-2010-11-317867
   PubMed Web of Science ®Google Scholar
• Osawa M, Masuda M, Harada N, Lopes RB, Fujiwara K. Tyrosine phosphorylation of platelet endothelial cell adhesion molecule-1 (PECAM-1, CD31) in mechanically stimulated vascular endothelial cells. Eur J Cell Biol 1997;723:p. 229–37.
   PubMed Web of Science ®Google Scholar
• Cao MY, Huber M, Beauchemin N, Famiglietti J, Albelda SM, Veillette A. Regulation of mouse PECAM-1 tyrosine phosphorylation by the Src and Csk families of protein-tyrosine kinases. J Biol Chem 1998;27325:p. 15765–72. https://doi.org/10.1074/jbc.273.25.15765
   PubMed Web of Science ®Google Scholar
• Sun QH, DeLisser HM, Zukowski MM, Paddock C, Albelda SM, Newman PJ. Individually distinct Ig homology domains in PECAM-1 regulate homophilic binding and modulate receptor affinity. J Biol Chem 1996;27119:p. 11090–8. https://doi.org/10.1074/jbc.271.19.11090
   PubMed Web of Science ®Google Scholar
• Privratsky JR, Paddock CM, Florey O, Newman DK, Muller WA, Newman PJ. Relative contribution of PECAM-1 adhesion and signaling to the maintenance of vascular integrity. J Cell Sci 2011;124Pt 9:p. 1477–85. https://doi.org/10.1242/jcs.082271
   PubMed Web of Science ®Google Scholar
• Sun J, Williams J, Yan H-C, Amin KM, Albelda SM, DeLisser HM. Platelet endothelial cell adhesion molecule-1 (PECAM-1) homophilic adhesion is mediated by immunoglobulin-like domains 1 and 2 and depends on the cytoplasmic domain and the level of surface expression. J Biol Chem 1996;27131:p. 18561–70. https://doi.org/10.1074/jbc.271.31.18561
   PubMed Web of Science ®Google Scholar
• Newton JP, Buckley CD, Jones EY, Simmons DL. Residues on both faces of the first immunoglobulin fold contribute to homophilic binding sites of PECAM-1/CD31. J Biol Chem 1997;27233:p. 20555–63. https://doi.org/10.1074/jbc.272.33.20555
   PubMed Web of Science ®Google Scholar
• Paddock C, Zhou D, Lertkiatmongkol P, Newman PJ, Zhu J. Structural basis for PECAM-1 homophilic binding. Blood 2016;1278:p. 1052–61. https://doi.org/10.1182/blood-2015-07-660092
   PubMed Web of Science ®Google Scholar
• Lee C, Liu A, Miranda-Ribera A, Hyun SW, Lillehoj EP, Cross AS, Passaniti A, Grimm PR, Kim B-Y, Welling PA, et al. NEU1 sialidase regulates the sialylation state of CD31 and disrupts CD31-driven capillary-like tube formation in human lung microvascular endothelia. J Biol Chem 2014;28913:9121–9135. https://doi.org/10.1074/jbc.M114.555888
   PubMed Web of Science ®Google Scholar
• Lertkiatmongkol P, Paddock C, Newman DK, Zhu J, Thomas MJ, Newman PJ. The role of sialylated glycans in human platelet endothelial cell adhesion molecule 1 (PECAM-1)-mediated trans homophilic interactions and endothelial cell barrier function. J Biol Chem 2016;29150:p. 26216–26225. https://doi.org/10.1074/jbc.M116.756502
   PubMed Web of Science ®Google Scholar
• DeLisser HM, Yan HC, Newman PJ, Muller WA, Buck CA, Albelda SM. Platelet/endothelial cell adhesion molecule-1 (CD31)-mediated cellular aggregation involves cell surface glycosaminoglycans. J Biol Chem 1993;26821:p. 16037–46. https://doi.org/10.1016/S0021-9258(18)82354-7
   PubMed Web of Science ®Google Scholar
• Buckley CD, Doyonnas R, Newton JP, Blystone SD, Brown EJ, Watt SM, Simmons DL. Identification of alpha v beta 3 as a heterotypic ligand for CD31/PECAM-1. J Cell Sci 1996;109Pt 2:p. 437–45.
   PubMed Web of Science ®Google Scholar
• Piali L, Hammel P, Uherek C, Bachmann F, Gisler RH, Dunon D, Imhof BA. CD31/PECAM-1 is a ligand for alpha v beta 3 integrin involved in adhesion of leukocytes to endothelium. J Cell Biol 1995;130(2):p. 451–60. https://doi.org/10.1083/jcb.130.2.451
   PubMed Web of Science ®Google Scholar
• Deaglio S, Morra M, Mallone R, Ausiello CM, Prager E, Garbarino G, Dianzani U, Stockinger H, Malavasi F. Human CD38 (ADP-ribosyl cyclase) is a counter-receptor of CD31, an Ig superfamily member. J Immunol 1998;160(1):p. 395–402.
   PubMed Web of Science ®Google Scholar
• Kuckleburg CJ, Newman PJ. Neutrophil proteinase 3 acts on protease-activated receptor-2 to enhance vascular endothelial cell barrier function. Arterioscler Thromb Vasc Biol 2013;332:p. 275–84. https://doi.org/10.1161/ATVBAHA.112.300474
   PubMed Web of Science ®Google Scholar
• Sachs UJ, Andrei-Selmer CL, Maniar A, Weiss T, Paddock C, Orlova VV, Choi EY, Newman PJ, Preer KT, Chavakis T, et al. The neutrophil-specific antigen CD177 is a counter-receptor for platelet endothelial cell adhesion molecule-1 (CD31). J Biol Chem 2007;28232:p. 23603–12. https://doi.org/10.1074/jbc.M701120200
   PubMed Web of Science ®Google Scholar
• Mori J, Pearce AC, Spalton JC, Grygielska B, Eble JA, Tomlinson MG, Senis YA, Watson SP. G6b-B inhibits constitutive and agonist-induced signaling by glycoprotein VI and CLEC-2. J Biol Chem 2008;28351:p. 35419–27. https://doi.org/10.1074/jbc.M806895200
   PubMed Web of Science ®Google Scholar
• de Vet EC, Aguado B, Campbell RD. G6b, a novel immunoglobulin superfamily member encoded in the human major histocompatibility complex, interacts with SHP-1 and SHP-2. J Biol Chem 2001;27645:p. 42070–6. https://doi.org/10.1074/jbc.M103214200
   PubMed Web of Science ®Google Scholar
• Senis YA, Antrobus R, Severin S, Parguiña AF, Rosa I, Zitzmann N, Watson SP, García A. Proteomic analysis of integrin alphaIIbbeta3 outside-in signaling reveals Src-kinase-independent phosphorylation of Dok-1 and Dok-3 leading to SHIP-1 interactions. J Thromb Haemost 2009;710:p. 1718–26. https://doi.org/10.1111/j.1538-7836.2009.03565.x
   PubMed Web of Science ®Google Scholar
• Mazharian A, Wang Y-J, Mori J, Bem D, Finney B, Heising S, Gissen P, White JG, Berndt MC, Gardiner EE, et al. Mice lacking the ITIM-containing receptor G6b-B exhibit macrothrombocytopenia and aberrant platelet function. Sci Signal 2012;5248:ra78. https://doi.org/10.1126/scisignal.2002936
   PubMed Web of Science ®Google Scholar
• Vogtle T, Sharma S, Mori J, Nagy Z, Semeniak D, Scandola C, Geer MJ, Smith CW, Lane J, Pollack S, et al. Heparan sulfates are critical regulators of the inhibitory megakaryocyte-platelet receptor G6b-B. Elife 2019;8. https://doi.org/10.7554/eLife.46840
   Google Scholar
• de Vet EC, Newland SAB, Lyons PA, Aguado B, Campbell RD. The cell surface receptor G6b, a member of the immunoglobulin superfamily, binds heparin. FEBS Lett 2005;57911:p. 2355–8. https://doi.org/10.1016/j.febslet.2005.03.032
   PubMed Web of Science ®Google Scholar
• Gashaw I, Ellinghaus P, Sommer A, Asadullah K. What makes a good drug target? Drug Discov Today 2011;1623–24:p. 1037–43. https://doi.org/10.1016/j.drudis.2011.09.007
   PubMed Web of Science ®Google Scholar
• Sardjono CT, Harbour S, Yip J, Paddock C, Tridandapani S, Newman P, Jackson D. Palmitoylation at Cys595 is essential for PECAM-1 localisation into membrane microdomains and for efficient PECAM-1-mediated cytoprotection. Thromb Haemost 2006;966:p. 756–66. https://doi.org/10.1160/TH06-08-0459
   PubMed Web of Science ®Google Scholar
• Rathore V, Stapleton MA, Hillery CA, Montgomery RR, Nichols TC, Merricks EP, Newman DK, Newman PJ. PECAM-1 negatively regulates GPIb/V/IX signaling in murine platelets. Blood 2003;10210:p. 3658–64. https://doi.org/10.1182/blood-2003-06-1888
   PubMed Web of Science ®Google Scholar
• Crockett J, Newman DK, Newman PJ. PECAM-1 functions as a negative regulator of laminin-induced platelet activation. J Thromb Haemost 2010;87:p. 1584–93. https://doi.org/10.1111/j.1538-7836.2010.03883.x
   PubMed Web of Science ®Google Scholar
• Jones CI, Sage T, Moraes LA, Vaiyapuri S, Hussain U, Tucker KL, Barrett NE, Gibbins JM. Platelet endothelial cell adhesion molecule-1 inhibits platelet response to thrombin and von Willebrand factor by regulating the internalization of glycoprotein Ib via AKT/glycogen synthase kinase-3/dynamin and integrin alphaIIbbeta3. Arterioscler Thromb Vasc Biol 2014;349:p. 1968–76. https://doi.org/10.1161/ATVBAHA.114.304097
   PubMed Web of Science ®Google Scholar
• Dhanjal TS, Ross EA, Auger JM, Mccarty OJT, Hughes CE, Senis YA,Buckley CD, Watson SP. Minimal regulation of platelet activity by PECAM-1. Platelets 2007;181:p. 56–67. https://doi.org/10.1080/09537100600881396
   PubMed Web of Science ®Google Scholar
• Jones KL, Hughan SC, Dopheide SM, Farndale RW, Jackson SP, Jackson DE. Platelet endothelial cell adhesion molecule-1 is a negative regulator of platelet-collagen interactions. Blood 2001;985:p. 1456–63. https://doi.org/10.1182/blood.V98.5.1456
   PubMed Web of Science ®Google Scholar
• Cicmil M, Thomas JM, Leduc M, Bon C, Gibbins JM. Platelet endothelial cell adhesion molecule-1 signaling inhibits the activation of human platelets. Blood 2002;991:137–144. https://doi.org/10.1182/blood.V99.1.137
   PubMed Web of Science ®Google Scholar
• Gurbel PA,Myat A, Kubica J, Tantry US. State of the art: oral antiplatelet therapy. JRSM Cardiovasc Dis 2016;5:2048004016652514.
   Web of Science ®Google Scholar
• Yeung J, Holinstat M. Newer agents in antiplatelet therapy: a review. J Blood Med 2012;3:33–42. https://doi.org/10.2147/JBM.S25421
   PubMedGoogle Scholar
• Jones CI, Barrett NE, Moraes LA, Gibbins JM, Jackson DE. Endogenous inhibitory mechanisms and the regulation of platelet function. Methods Mol Biol 2012;788:341–366.
   PubMedGoogle Scholar
• Novinska MS, Pietz BC, Ellis TM, Newman DK, Newman PJ. The alleles of PECAM-1. Gene 2006;3761:95–101. https://doi.org/10.1016/j.gene.2006.02.016
   PubMed Web of Science ®Google Scholar
• Li G, Han ZL, Dong HG, Zhang X, Kong XQ, Jin X. Platelet endothelial cell adhesion molecule-1 gene 125C/G polymorphism is associated with deep vein thrombosis. Mol Med Rep 2015;122:2203–2210. https://doi.org/10.3892/mmr.2015.3586
   PubMed Web of Science ®Google Scholar
• Dhanjal TS, Pendaries C, Ross EA, Larson MK, Protty MB, Buckley CD, Watson SP. A novel role for PECAM-1 in megakaryocytokinesis and recovery of platelet counts in thrombocytopenic mice. Blood 2007;10910:4237–4244. https://doi.org/10.1182/blood-2006-10-050740
   PubMed Web of Science ®Google Scholar
• Mahooti S, Graesser D, Patil S, Newman P, Duncan G, Mak T, Madri JA. PECAM-1 (CD31) expression modulates bleeding time in vivo. Am J Pathol 2000;1571:75–81. https://doi.org/10.1016/S0002-9440(10)64519-1
   PubMed Web of Science ®Google Scholar
• Newland SA, Macaulay IC, Floto AR, de Vet EC, Ouwehand WH, Watkins NA, Lyons PA, Campbell DR. The novel inhibitory receptor G6B is expressed on the surface of platelets and attenuates platelet function in vitro. Blood 2007;10911:4806–4809. https://doi.org/10.1182/blood-2006-09-047449
   PubMed Web of Science ®Google Scholar
• Hofmann I, Geer MJ, Vögtle T, Crispin A, Campagna DR, Barr A, Calicchio ML, Heising S, van Geffen JP, Kuijpers MJE, et al. Congenital macrothrombocytopenia with focal myelofibrosis due to mutations in human G6b-B is rescued in humanized mice. Blood 2018;13213:1399–1412. https://doi.org/10.1182/blood-2017-08-802769
   PubMed Web of Science ®Google Scholar
• Gurevich EV, Gurevich VV. Therapeutic potential of small molecules and engineered proteins. Handb Exp Pharmacol 2014;219:1–12.
   PubMedGoogle Scholar
• Buchwald P. Small-molecule protein-protein interaction inhibitors: therapeutic potential in light of molecular size, chemical space, and ligand binding efficiency considerations. IUBMB Life 2010;6210:724–731. https://doi.org/10.1002/iub.383
   PubMed Web of Science ®Google Scholar
• Faulds D, Sorkin EM. Abciximab (c7E3 Fab). A review of its pharmacology and therapeutic potential in ischaemic heart disease. Drugs 1994;484:583–598. https://doi.org/10.2165/00003495-199448040-00007
   PubMed Web of Science ®Google Scholar
• Chames P, Van Regenmortel M, Weiss E, Baty D. Therapeutic antibodies: successes, limitations and hopes for the future. Br J Pharmacol 2009;1572:220–233. https://doi.org/10.1111/j.1476-5381.2009.00190.x
   PubMed Web of Science ®Google Scholar
• Nurbhai S, Roberts KJ, Carlton TM, Maggiore L, Cubitt MF, Ray KP, Reckless J, Mohammed H, Irving P, MacDonald TT, et al. Oral anti-tumour necrosis factor domain antibody V565 provides high intestinal concentrations, and reduces markers of inflammation in ulcerative colitis patients. Sci Rep 2019;91:14042. https://doi.org/10.1038/s41598-019-50545-x
   PubMed Web of Science ®Google Scholar
• Duggan S. Caplacizumab: first global approval. Drugs 2018;7815:1639–1642. https://doi.org/10.1007/s40265-018-0989-0
   PubMed Web of Science ®Google Scholar
• Tiede C, Bedford R, Heseltine SJ, Smith G, Wijetunga I, Ross R, AlQallaf D, Roberts AP, Balls A, Curd A, et al. Affimer proteins are versatile and renewable affinity reagents. Elife 2017;6. https://doi.org/10.7554/eLife.24903
   PubMed Web of Science ®Google Scholar
• Kearney KJ, Pechlivani N, King R, Tiede C, Phoenix F, Cheah R, Macrae FL, Simmons KJ, Manfield IW, Smith KA, et al. Affimer proteins as a tool to modulate fibrinolysis, stabilize the blood clot, and reduce bleeding complications. Blood 2019;13311:1233–1244. https://doi.org/10.1182/blood-2018-06-856195
   PubMed Web of Science ®Google Scholar
• Ungerer M, Rosport K, Bültmann A, Piechatzek R, Uhland K, Schlieper P, Gawaz M, Münch G. Novel antiplatelet drug revacept (Dimeric Glycoprotein VI-Fc) specifically and efficiently inhibited collagen-induced platelet aggregation without affecting general hemostasis in humans. Circulation 2011;12317:1891–1899. https://doi.org/10.1161/CIRCULATIONAHA.110.980623
   PubMed Web of Science ®Google Scholar
• Lebozec K, Jandrot-Perrus M, Avenard G, Favre-Bulle O, Billiald P. Design, development and characterization of ACT017, a humanized Fab that blocks platelet’s glycoprotein VI function without causing bleeding risks. MAbs 2017;96:945–958. https://doi.org/10.1080/19420862.2017.1336592
   PubMed Web of Science ®Google Scholar
• Voors-Pette C, Lebozec K, Dogterom P, Jullien L, Billiald P, Ferlan P, Renaud L, Favre-Bulle O, Avenard G, Machacek M, et al. Safety and tolerability, pharmacokinetics, and pharmacodynamics of ACT017, an antiplatelet GPVI (glycoprotein VI) Fab. Arterioscler Thromb Vasc Biol 2019;395:956–964. https://doi.org/10.1161/ATVBAHA.118.312314
   PubMed Web of Science ®Google Scholar