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DOI: 10.1055/s-0037-1615854
The Glycoprotein Ib-IX-V Complex in Platelet Adhesion and Signaling
Publication History
Publication Date:
09 December 2017 (online)
![](https://www.thieme-connect.de/media/10.1055-s-00035024/199902/lookinside/thumbnails/10-1055-s-0037-1615854-1.jpg)
Introduction
Thrombosis can result in unstable angina, acute myocardial infarction, or stroke, all major causes of death in the Western world. Circulating platelets become adherent and form an occlusive thrombus, either by exposure to sclerotic lesions following plaque rupture or in response to pathological shear stress in obstructed coronary arteries. This process parallels normal haemostasis, where platelets adhere to the subendothelium at sites of vascular injury, become activated, and recruit additional platelets to the developing thrombus. At high shear, thrombus formation is initiated by a specific platelet membrane adhesion receptor, the glycoprotein (GP) Ib-IX-V complex, which binds the adhesive glycoprotein, von Willebrand factor (vWF), in the vessel wall or plasma. Recent evidence also suggests that platelet adhesion to endothelial cells and leukocytes may be involved in atherogenesis, thrombosis, and inflammation. Preliminary findings indicate that GP Ib-IX-V specifically recognizes P-selectin, a member of the selectin superfamily, an interaction that may, at least partially, regulate platelet-endothelial cell adhesion. This review focuses on recent advances in understanding structure-activity relationships of GP Ib-IX-V.
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References
- 1 Andrews RK, López JA, Berndt MC. Molecular mechanisms of platelet adhesion and activation. Int J Biochem Cell Biol. 1997; 29: 91-105.
- 2 López JA. The platelet glycoprotein Ib-IX complex. Blood Coagul Fibrinolysis. 1994; 5: 97-119.
- 3 Kroll MH, Hellums JD, McIntyre LV, Schafer AI, Moake JL. Platelets and shear stress. Blood 1996; 88: 1525-1541.
- 4 Weiss HJ. Flow-related platelet deposition on subendothelium. Thromb Haemostas. 1995; 74: 117-122.
- 5 Ware J. Molecular analysis of the platelet glycoprotein Ib-IX-V receptor. 1998 79. 466-478.
- 6 Watson SP, Gibbins J. Collagen receptor signaling in platelets: extending the role of the ITAM. Immunol Today. 1998; 19: 260-264.
- 7 Fujimura Y, Kawasaki T, Titani K. Snake venom proteins modulating the interaction between von Willebrand factor and platelet glycoprotein Ib. Thromb Haemostas. 1997; 76: 633-639.
- 8 Ruggeri ZM. Mechanisms initiating platelet thrombus formation. Thromb Haemostas. 1997; 78: 611-616.
- 9 Andrews RK, Berndt MC. Adhesion-dependent signaling and the initiation of haemostasis and thrombosis. Histol Histopath. 1998; 13: 837-844.
- 10 Fox JEB, Meyer SC. In: Berndt MC. ed. Platelets, Thrombosis and the Vessel Wall. Berndt MC. (ed). Reading, PA: Harwood Academic Publishers; Reading In press.
- 11 Du X, Ginsberg MH. Integrin αIIbβ3 and platelet function. Thromb Haemostas. 1997; 78: 96-100.
- 12 Savage B, Salvidar E, Ruggeri ZM. Initiation of platelet adhesion by arrest onto fibrinogen or translocation on von Willebrand factor. Cell. 1996; 84: 289-297.
- 13 Savage B, Almus-Jacobs F, Ruggeri ZM. Synergy of multiple substrate-receptor interactions in platelet thrombus formation under flow. Cell. 1998; 94: 657-666.
- 14 Goto S, Ikeda Y, Salvidar E, Ruggeri ZM. Distinct mechanisms of platelet aggregation as a consequence of different shearing flow conditions. J Clin Invest. 1998; 101: 479-486.
- 15 Fredrickson BJ, Dong J-F, McIntire LV, López JA. Shear-dependent rolling on von Willebrand factor of mammalian cells expressing the platelet glycoprotein Ib-IX-V complex. Blood 1998; 92: 3684-3693.
- 16 Ward CM, Andrews RK, Smith AI, Berndt MC. Mocarhagin, a novel cobra venom metalloproteinase, cleaves the platelet von Willebrand factor receptor glycoprotein Ibα. Binding site for von Willebrand factor and α-thrombin. Biochemistry. 1996; 35: 4929-4938.
- 17 Dong J-F, Li CQ, López JA. Tyrosine sulfation of the glycoprotein Ib-IX complex: Identification of sulfated residues and effect on ligand binding. Biochemistry. 1994; 33: 13946-13953.
- 18 Marchese P, Murata M, Mazzucato M, Pradella P, De Marco L, Ware J, Ruggeri ZM. Identification of three tyrosine residues of glycoprotein Ibα with distinct roles in von Willebrand factor and α-thrombin binding. J Biol Chem. 1995; 270: 9571-9578.
- 19 López JA, Andrews RK, Afshar-Kharghan V, Berndt MC. Bernard-Soulier syndrome. Blood 1998; 91: 4397-4418.
- 20 Dong J-F, Gao S, López JA. Synthesis, assembly, and intracellular transport of the platelet glycoprotein Ib-IX-V complex. J Biol Chem. 1998; 273: 31449-31454.
- 21 Meyer SC, Sanan DA, Fox JEB. Role of actin-binding protein in insertion of adhesion receptors into the membrane. J Biol Chem. 1998; 273: 3013-3020.
- 22 Budarf ML, Konkle BA, Ludlow LB, Michaud D, Li M, Yamashiro DJ, McDonald-McGinn D, Zackai EH, Driscoll DA. Identification of a patient with Bernard-Soulier syndrome and a deletion in the DiGeorge/velo-cardio-facial chromosomal region in 22q11.2. Hum Mol Genet. 1995; 4: 763-766.
- 23 Kunishima S, López JA, Kobayashi S, Imai N, Kamiya T, Saito H, Naoe T. Missense mutations of the glycoprotein (GP) Ibβ gene impairing the GPIb α/β disulfide linkage in a family with giant platelet disorder. Blood 1997; 89: 2404-2412 1997.
- 24 Miller JL. Platelet-type von Willebrand disease. Thromb Haemostas. 1996; 75: 865-869.
- 25 Murata M, Ware J, Ruggeri ZM. Site-directed mutagenesis of a soluble recombinant fragment of platelet glycoprotein Ibα demonstrating negatively charged residues involved in von Willebrand factor binding. J Biol Chem. 1990; 266: 15474-15480.
- 26 Berndt MC, Shen Y, Romo G, Kenny DA, López JA, Andrews RK. Identification of monoclonal antibody epitopes and the ristocetin-dependent binding site on the α-chain of the platelet GP Ib-IX-V complex using canine-human chimaeras. Blood 1998; 92: 703a.
- 27 Mazzucato M, De Marco L, Masotti A, Pradella P, Bahou WF, Ruggeri ZM. Characterization of the initial α-thrombin interaction with glycoprotein Ibα in relation to platelet activation. J Biol Chem. 1998; 273: 1880-1887.
- 28 Dong J-F, Sae-Tung G, López JA. Role of glycoprotein V in the formation of the platelet high-affinity thrombin-binding site. Blood 1997; 89: 4355-4363.
- 29 Xu WF, Andersen H, Whitmore TE, Presnell SR, Yee DP, Ching A, Gilbert T, Davie EW, Foster DC. Cloning and characterization of human protease-activated receptor 4. Proc Natl Acad Sci USA. 1998; 95: 6642-6646.
- 30 Kahn ML, Zheng Y-W, Huang W, Bigornia V, Zeng D, Moff S, Farese Jr. RV, Tam C, Coughlin SR. A dual thrombin receptor system for platelet activation. Nature 1998; 394: 690-694.
- 31 Peng M, Lu W, Kirby EP. Characterization of three alboaggregins purified from Trimeresurus albolabris venom. Thromb Haemostas. 1992; 67: 702-707.
- 32 Andrews RK, Kroll MH, Ward CM, Rose JW, Scarborough RM, Smith AI, López JA, Berndt MC. Binding of a novel 50-kilodalton alboaggregin from Trimeresurus albolabris and related viper venom proteins to the platelet membrane glycoprotein Ib-IX-V complex. Effect on platelet aggregation and glycoprotein Ib-mediated platelet activation. Biochemistry. 1996; 35: 12629-12639.
- 33 Kowalska MA, Tan L, Holt JC, Peng M, Karczewski J, Calvete JJ, Niewiarowski S. Alboaggregins A and B. Structure and interaction with human platelets. Thromb Haemostas. 1998; 79: 609-613.
- 34 Hamako J, Matsui T, Nishida S, Nomura S, Fujimura Y, Ito M, Ozeki Y, Titani K. Purification and characterization of kaouthiagin, a von Willebrand factor-binding and -cleaving metalloproteinase from Naja kaouthia cobra venom. Thromb Haemostas. 1998; 80: 499-505.
- 35 Frenette PS, Johnson RC, Hynes RO, Wagner DD. Platelets roll on stimulated endothelium in vivo: an interaction mediated by endothelial P-selectin. Proc Natl Acad Sci USA. 1995; 92: 7450-7454.
- 36 Frenette PS, Moyna C, Hartwell DW, Lowe JB, Hynes RO, Wagner DD. Platelet-endothelial interactions in inflamed mesenteric venules. Blood 1998; 91: 1318-1324.
- 37 Bombeli T, Schwartz BR, Harlan JM. Adhesion of activated platelets to endothelial cells: evidence for a GPIIbIIIa-dependent bridging mechanism and novel roles for endothelial intercellular adhesion molecule 1 (ICAM-1), αvbβ3 integrin, and GP Ibα. J Exp Med. 1998; 187: 329-339.
- 38 Ross R. Cell biology of atherosclerosis. Ann Rev Physiol. 1995; 57: 791-804.
- 39 Kuijper PHM, Torres G, van der Linden JAM, Lammers J-WJ, Sixma JJ, Koenderman L, Zwaginga JJ. Platelet-dependent primary haemostasis promotes selectin- and integrin-mediated neutrophil adhesion to damaged endothelium under flow conditions. Blood 1996; 87: 3271-3281.
- 40 Springer TA. Traffic signals on endothelium for lymphocyte recirculation and leukocyte emigration. Ann Rev Physiol. 1995; 57: 827-872.
- 41 Sako D, Chang XJ, Barone KM, Vachino G, White HM, Shaw GD, Veldman GM, Bean KM, Ahern TJ, Furie B, Cumming DA, Larsen GR. Expression cloning of a functional glycoprotein ligand for P-selectin. Cell. 1993; 75: 1179-1186.
- 42 Sako D, Comess KM, Barone KM, Camphausen RT, Cumming DA, Shaw GD. A sulfated peptide segment at the amino terminus of PSGL-1 is critical for P-selectin binding. Cell. 1995; 83: 323-331.
- 43 De Luca M, Dunlop LC, Andrews RK, Flannery JV, Ettling R, Cumming DA, Veldman GM, Berndt MC. A novel cobra venom metalloproteinase, mocarhagin, cleaves a ten amino acid peptide from the mature N-terminus of P-selectin glycoprotein ligand receptor, PSGL-1, and abolishes P-selectin binding. J Biol Chem. 1995; 270: 26734-26737.
- 44 Tu L, Chen A, Delahunty MD, Moore KL, Watson SR, McEver RP, Tedder TF. L-selectin binds to P-selectin glycoprotein ligand-1 on leukocytes: interactions between the lectin, epidermal growth factor, and consensus repeat domains of the selectins determine ligand binding specificity. J Immunol. 1996; 157: 3995-4004.
- 45 Spertini O, Cordey AS, Monai N, Giuffre L, Schapira M. P-selectin glycoprotein ligand 1 is a ligand for L-selectin on neutrophils, monocytes, and CD34+ haematopoietic progenitor cells. J Cell Biol. 1996; 135: 523-531.
- 46 Guyer DA, Moore KL, Lynam EB, Schammel CM, Rogelj S, McEver RP, Sklar LA. P-selectin glycoprotein ligand-1 (PSGL-1) is a ligand for L-selectin in neutrophil aggregation. Blood 1996; 88: 2415-2421.
- 47 Walcheck B, Moore KL, McEver RP, Kishimoto TK. Neutrophil-neutrophil interactions under hydrodynamic shear stress involve L-selectin and PSGL-1. A mechanism that amplifies initial leukocyte accumulation of P-selectin in vitro. J Clin Invest. 1996; 98: 1081-1087.
- 48 López JA, Romo GM, Dong J-F, Schade A, Kansas GS, McIntire LV, Berndt MC. The glycoprotein Ib-IX-V complex is a platelet counter-receptor for P-selectin. Blood 1998; 92: 703a.
- 49 Valles J, Santos MT, Marcus AJ, Safier LB, Broekman MJ, Islam N, Ullman HL, Aznar J. Downregulation of human platelet reactivity by neutrophils. Participation of lipoxygenase derivatives and adhesive proteins. J Clin Invest. 1993; 92: 1357-1365.
- 50 Varon D, Jackson DE, Shenkman B, Dardik R, Tamarin I, Savion N, Newman PJ. Platelet/endothelial cell adhesion molecule-1 serves as a costimulatory agonist receptor that modulates integrin-dependent adhesion and aggregation of human platelets. Blood 1998; 91: 500-507.
- 51 Diacovo TG, deFougerolles AR, Bainton DF, Springer TA. A functional integrin ligand on the surface of platelets: intercellular adhesion molecule-2. J Clin Invest. 1994; 94: 1243-1251.
- 52 Cunningham JG, Meyer SC, Fox JEB. The cytoplasmic domain of the α-subunit of glycoprotein (GP) Ib mediates attachment of the entire GP Ib-IX complex to the cytoskeleton and regulates von Willebrand Factor-induced changes in cell morphology. J Biol Chem. 1996; 271: 11581-11587.
- 53 Andrews RK, Fox JEB. Identification of a region from the cytoplasmic domain of the platelet membrane GP Ib-IX complex that binds to purified actin-binding protein. J Biol Chem. 1992; 267: 18605-18611.
- 54 Du X, Harris SJ, Tetaz TJ, Ginsberg MH, Berndt MC. Association of a phospholipase A2 (14.3.3 protein) with the platelet glycoprotein Ib-IX complex. J Biol Chem. 1994; 269: 18287-18290.
- 55 Du X, Fox JE, Pei S. Identification of a binding sequence for the 14-3-3 protein within the cytoplasmic domain of the adhesion receptor, platelet glycoprotein Ibα. J Biol Chem. 1996; 271: 7362-7367.
- 56 Andrews RK, Harris SJ, McNally T, Berndt MC. Binding of purified 14-3-3 ζ signaling protein to discrete amino acid sequences within the cytoplasmic domain of the platelet membrane glycoprotein Ib-IX-V complex. Biochemistry. 1998; 37: 638-647.
- 57 Calverly DC, Kavanagh TJ, Roth GJ. Human signaling protein 14-3-3ζ interacts with platelet glycoprotein Ib subunits GP Ibα and Ibβ. Blood 1998; 91: 1295-1303.
- 58 Aitken A. 14-3-3 and its possible role in coordinating multiple signaling pathways. Trends Cell Biol. 1996; 6: 341-347.
- 59 Muslin AJ, Tanner JW, Allen PM, Shaw AS. Interaction of 14-3-3 with signaling proteins is mediated by the recognition of phosphoserine. Cell. 1996; 84: 889-897.
- 60 Zha J, Harada H, Yang E, Jockel J, Korsmeyer SJ. Serine phosphorylation of death agonist BAD in response to survival factor results in binding to 14-3-3 not BCL-XL . Cell. 1996; 87: 619-628.
- 61 Liu Y-C, Liu Y, Elly C, Yoshida H, Lipkowitz S, Altman A. Serine phosphorylation of cbl induced by phorbol ester enhances its association with 14-3-3 proteins in T cells via a novel serine-rich 14-3-3–binding motif. J Biol Chem. 1997; 272: 9979-9985.
- 62 Craparo A, Freund R, Gustafson TA. 14-3-3 (ε) interacts with the insulin-like growth factor 1 receptor substrate 1 in a phosphoserine-dependent manner. J Biol Chem. 1997; 272: 11663-11669.
- 63 Ogihara T, Isobe T, Ichimura T, Taoka M, Funaki M, Sakoda H, Onishi Y, Inukai K, Anai M, Fukushima Y, Kikuchi Y, Oka Y, Asano T. 14-3-3 protein binds to insulin receptor substrate-1, one of the binding sites of which is in the phosphotyrosine binding domain. J Biol Chem. 1997; 272: 25267-25273.
- 64 Gu M, Du X. A novel ligand-binding site in the ζ-form 14-3-3 protein recognizing the platelet glycoprotein Ibα and distinct from the c-raf-binding site. J Biol Chem. 1998; 273: 33465-33471.
- 65 Jackson SP, Schoenwaelder SM, Yan Y, Rabinowitz I, Salem HH, Mitchell CA. Adhesion receptor activation of phosphatidylinositol 3-kinase: von Willebrand factor stimulates the cytoskeletal association and activation of phosphatidylinositol 3-kinase and pp60src in human platelets. J Biol Chem. 1994; 269: 27093-27099.
- 66 Asazuma N, Ozaki Y, Satoh K, Handa M, Fujimura Y, Miura S, Kume S. Glycoprotein Ib-von Willebrand factor interactions activate tyrosine kinases in human platelets. Blood 1997; 90: 4789-4798.