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Gene Review

ITGA2B  -  integrin, alpha 2b (platelet glycoprotein...

Homo sapiens

Synonyms: BDPLT16, BDPLT2, CD41, CD41B, GP2B, ...
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Disease relevance of ITGA2B


Psychiatry related information on ITGA2B

  • We examined the effects of glycoprotein IIb/IIIa (GPIIb/IIIa) antagonists c7E3 Fab and DMP728 on the development of platelet prothrombinase (PT) activity. c7E3 Fab dose-dependently inhibited the rate of thrombin-stimulated thrombin generation over a 1-minute reaction time [5].
  • PlA2 carriers had a higher degree of GPIIb/IIIa activation (P = 0.05) and P-selectin expression (P = 0.02) during the overall study time course and a lower antiplatelet effect to a 300 mg clopidogrel loading-dose up to 24 h following intervention (P < 0.05) [6].
  • The findings indicate that smoking is associated with increased platelet serotonin receptor density and with increased GPIIb/IIIa receptor binding, although these 2 factors are not related to each other or to depressive symptoms among smokers [7].
  • In conclusion, this study shows that PFA-100 may be helpful in the decision making for additional antiaggregant therapy before PTCA or in monitoring long-term GPIIb/IIIa receptor antagonist treatment [8].
  • Specifically, for major depression the GTA haplotype has an OR of 1.59 (p=0.01) and for bipolar disorder an OR of 1.89 (p=0.03) [9].

High impact information on ITGA2B

  • The failure of thrombin to support 125I-vWF binding to thrombasthenic platelets, which contain GPIb but lack GPIIb/IIIa, suggests that the mechanism of this interaction may be distinct from ristocetin-induced binding [10].
  • An affinity matrix made of an insolubilized heptapeptide containing the Arg-Gly-Asp sequence selectively binds the platelet membrane glycoprotein IIb/IIIa from detergent extracts of platelets [11].
  • The topographic relationships of platelet membrane glycoprotein IIb and glycoprotein IIIa have been studied in stimulated and unstimulated human platelets using immunoelectron microscopy [12].
  • We conclude that thrombin generation initiated by tissue factor in the presence of platelets is significantly inhibited by c7E3 Fab, most likely in part through both GPIIb/IIIa and alpha v beta 3 blockade, and that this effect may contribute to its antithrombotic properties [13].
  • The murine/human chimeric monoclonal antibody fragment (c7E3 Fab) blocks GPIIb/IIIa and alpha v beta 3 receptors, inhibits platelet aggregation, and decreases the frequency of ischemic events after coronary artery angioplasty in patients at high risk of suffering such events [13].

Chemical compound and disease context of ITGA2B


Biological context of ITGA2B


Anatomical context of ITGA2B


Associations of ITGA2B with chemical compounds

  • Regions amino-terminal to the calcium-binding domains of GPIIb may play a heretofore unappreciated role in integrin subunit association [21].
  • Platelet and endothelial cell GPIIb alpha (but not GPIIIa) showed an increased electrophoretic mobility in Ca2+ -containing versus EDTA-containing gels, implying a Ca2+ -GPIIb alpha interaction [24].
  • The Baka form of GPIIb encodes an isoleucine at this position, whereas the Bakb allele contains a serine [25].
  • Although activated by several platelet agonists, including thrombin and thromboxane A(2), the contribution of the G(12/13) signaling pathway to GPIIb/IIIa activation has not been investigated [26].
  • Removal of the negatively charged carboxyl group of Asp418 GPIIb, creating Ala418 GPIIb, rescued intracellular transport and surface expression of the integrin complex [27].

Physical interactions of ITGA2B


Regulatory relationships of ITGA2B

  • The results of the present study demonstrate that independent modulation of vWF and fibrinogen binding to stimulated platelets can be attained with monoclonal antibodies directed against distinct epitopes of GPIIb/IIIa [28].
  • Extracellular signal-regulated kinase induces the megakaryocyte GPIIb/CD41 gene through MafB/Kreisler [32].
  • GPIIb/IIIa blockade enhanced ADP- or TRAP-induced leukocyte CD11b expression, but not the response to PAF [33].
  • In addition, either recombinant human IFN-gamma or TNF-alpha alone is capable of inducing CD41 and CD42 expression on HIMeg-1 cells [34].
  • Overexpression of PU.1/Spi-1 was further shown to enhance GPIIb promoter activity in the absence and presence of TPO [35].

Co-localisations of ITGA2B

  • We used specific antibodies in granulocyte macrophage colony-stimulating factor-treated neutrophils and observed that acquired GPIIb/IIIa receptors co-localized with beta2-integrins and cooperated in NF-kappaB activation [36].

Other interactions of ITGA2B

  • None of them reacted with dissociated GPIIb or GPIIIa [28].
  • Previously, we have shown that, when bound to glycoprotein IIb (GPIIb), calcium- and integrin-binding protein (CIB) regulates platelet spreading on immobilized fibrinogen (Fg) [37].
  • Further, confirmation of these data in the platelet system indicates that CIB and FAK associate throughout all stages of platelet spreading but only on Fg binding to GPIIb/IIIa [37].
  • Therefore the epitope of MAb 9 is located within aa 1698-1773 of the vWF subunit, which includes the RGD sequence implicated in the binding of adhesive proteins of GPIIb/IIIa [38].
  • Platelet activation was characterized by flow cytometric measurement of GPIIb/IIIa and GMP-140 in whole blood and washed platelets suspensions, with antihuman fluorescent monoclonal antibodies [39].

Analytical, diagnostic and therapeutic context of ITGA2B

  • Polymerase chain reaction (PCR) studies using platelet RNA and oligonucleotides directed to both the 5' and 3' ends of the GPIIb cDNA sequence easily detected GPIIb transcript, suggesting that the genomic deletion of exons 2-9 does not significantly decrease the level of the GPIIb mRNA [20].
  • Initial Western blot analysis of platelet proteins from this patient did not detect any GPIIb, but did detect small amounts of GPIIIa of normal mobility [20].
  • Northern blot analysis showed a approximately 3.4-kb GPIIb mRNA in HEL cells [2].
  • Genomic Southern blot studies demonstrated a deletion in the GPIIb gene of approximately 4.5 kilobasepairs (kb) [20].
  • Analysis by flow cytometry failed to demonstrate detectable amounts of GPIIb or GPIIb/IIIa complex on the surface of cells transfected with each mutation, but immunohistochemical staining revealed their intracellular presence [14].


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  2. Platelet glycoprotein IIb. Chromosomal localization and tissue expression. Bray, P.F., Rosa, J.P., Johnston, G.I., Shiu, D.T., Cook, R.G., Lau, C., Kan, Y.W., McEver, R.P., Shuman, M.A. J. Clin. Invest. (1987) [Pubmed]
  3. Calpain proteolysis of von Willebrand factor enhances its binding to platelet membrane glycoprotein IIb/IIIa: an explanation for platelet aggregation in thrombotic thrombocytopenic purpura. Moore, J.C., Murphy, W.G., Kelton, J.G. Br. J. Haematol. (1990) [Pubmed]
  4. Gene frequencies of the human platelet antigen-3 in different populations. Wiwanitkit, V. Clin. Appl. Thromb. Hemost. (2005) [Pubmed]
  5. Glycoprotein IIb/IIIa receptor antagonists inhibit the development of platelet procoagulant activity. Pedicord, D.L., Thomas, B.E., Mousa, S.A., Dicker, I.B. Thromb. Res. (1998) [Pubmed]
  6. PlA polymorphism and platelet reactivity following clopidogrel loading dose in patients undergoing coronary stent implantation. Angiolillo, D.J., Fernandez-Ortiz, A., Bernardo, E., Alfonso, F., Sabaté, M., Fernández, C., Stranieri, C., Trabetti, E., Pignatti, P.F., Macaya, C. Blood Coagul. Fibrinolysis (2004) [Pubmed]
  7. Increased serotonin receptor density and platelet GPIIb/IIIa activation among smokers. Markovitz, J.H., Tolbert, L., Winders, S.E. Arterioscler. Thromb. Vasc. Biol. (1999) [Pubmed]
  8. Use of the PFA-100 apparatus to assess platelet function in patients undergoing PTCA during and after infusion of c7E3 Fab in the presence of other antiplatelet agents. Hézard, N., Metz, D., Nazeyrollas, P., Droulle, C., Elaerts, J., Potron, G., Nguyen, P. Thromb. Haemost. (2000) [Pubmed]
  9. Polymorphisms in wolframin (WFS1) gene are possibly related to increased risk for mood disorders. Koido, K., Kõks, S., Nikopensius, T., Maron, E., Altmäe, S., Heinaste, E., Vabrit, K., Tammekivi, V., Hallast, P., Kurg, A., Shlik, J., Vasar, V., Metspalu, A., Vasar, E. Int. J. Neuropsychopharmacol. (2005) [Pubmed]
  10. Inhibition of von Willebrand factor-platelet interaction by fibrinogen. Piétu, G., Cherel, G., Marguerie, G., Meyer, D. Nature (1984) [Pubmed]
  11. Platelet membrane glycoprotein IIb/IIIa: member of a family of Arg-Gly-Asp--specific adhesion receptors. Pytela, R., Pierschbacher, M.D., Ginsberg, M.H., Plow, E.F., Ruoslahti, E. Science (1986) [Pubmed]
  12. Thrombin-induced platelet membrane glycoprotein IIb and IIIa complex formation. An electron microscope study. Polley, M.J., Leung, L.L., Clark, F.Y., Nachman, R.L. J. Exp. Med. (1981) [Pubmed]
  13. Inhibition of platelet-mediated, tissue factor-induced thrombin generation by the mouse/human chimeric 7E3 antibody. Potential implications for the effect of c7E3 Fab treatment on acute thrombosis and "clinical restenosis". Reverter, J.C., Béguin, S., Kessels, H., Kumar, R., Hemker, H.C., Coller, B.S. J. Clin. Invest. (1996) [Pubmed]
  14. Major mutations in calf-1 and calf-2 domains of glycoprotein IIb in patients with Glanzmann thrombasthenia enable GPIIb/IIIa complex formation, but impair its transport from the endoplasmic reticulum to the Golgi apparatus. Rosenberg, N., Yatuv, R., Sobolev, V., Peretz, H., Zivelin, A., Seligsohn, U. Blood (2003) [Pubmed]
  15. Anti-thrombotic effects and bleeding risk of AJvW-2, a monoclonal antibody against human von Willebrand factor. Kageyama, S., Yamamoto, H., Nagano, M., Arisaka, H., Kayahara, T., Yoshimoto, R. Br. J. Pharmacol. (1997) [Pubmed]
  16. Lotrafiban: an oral platelet glycoprotein IIb/IIIa blocker. Liu, F., Craft, R.M., Morris, S.A., Carroll, R.C. Expert opinion on investigational drugs. (2000) [Pubmed]
  17. Antithrombotic properties of L-cysteine, N-(mercaptoacetyl)-D-Tyr-Arg-Gly-Asp-sulfoxide (G4120) in a hamster platelet-rich femoral vein thrombosis model. Imura, Y., Stassen, J.M., Bunting, S., Stockmans, F., Collen, D. Blood (1992) [Pubmed]
  18. Blockade of GPIIb/IIIa by eptifibatide and tirofiban does not alter tissue factor induced thrombin generation in human endotoxemia. Derhaschnig, U., Pachinger, C., Schweeger-Exeli, I., Marsik, C., Jilma, B. Thromb. Haemost. (2003) [Pubmed]
  19. An association of candidate gene haplotypes and bleeding severity in von Willebrand disease (VWD) type 1 pedigrees. Kunicki, T.J., Federici, A.B., Salomon, D.R., Koziol, J.A., Head, S.R., Mondala, T.S., Chismar, J.D., Baronciani, L., Canciani, M.T., Peake, I.R. Blood (2004) [Pubmed]
  20. A deletion in the gene for glycoprotein IIb associated with Glanzmann's thrombasthenia. Burk, C.D., Newman, P.J., Lyman, S., Gill, J., Coller, B.S., Poncz, M. J. Clin. Invest. (1991) [Pubmed]
  21. Glanzmann thrombasthenia resulting from a single amino acid substitution between the second and third calcium-binding domains of GPIIb. Role of the GPIIb amino terminus in integrin subunit association. Wilcox, D.A., Paddock, C.M., Lyman, S., Gill, J.C., Newman, P.J. J. Clin. Invest. (1995) [Pubmed]
  22. Structure of platelet glycoprotein IIIa. A common subunit for two different membrane receptors. Zimrin, A.B., Eisman, R., Vilaire, G., Schwartz, E., Bennett, J.S., Poncz, M. J. Clin. Invest. (1988) [Pubmed]
  23. Glanzmann thrombasthenia secondary to a Gly273-->Asp mutation adjacent to the first calcium-binding domain of platelet glycoprotein IIb. Poncz, M., Rifat, S., Coller, B.S., Newman, P.J., Shattil, S.J., Parrella, T., Fortina, P., Bennett, J.S. J. Clin. Invest. (1994) [Pubmed]
  24. Platelet glycoproteins IIb and IIIa: evidence for a family of immunologically and structurally related glycoproteins in mammalian cells. Charo, I.F., Fitzgerald, L.A., Steiner, B., Rall, S.C., Bekeart, L.S., Phillips, D.R. Proc. Natl. Acad. Sci. U.S.A. (1986) [Pubmed]
  25. Polymorphism of human platelet membrane glycoprotein IIb associated with the Baka/Bakb alloantigen system. Lyman, S., Aster, R.H., Visentin, G.P., Newman, P.J. Blood (1990) [Pubmed]
  26. Coordinated signaling through both G12/13 and G(i) pathways is sufficient to activate GPIIb/IIIa in human platelets. Dorsam, R.T., Kim, S., Jin, J., Kunapuli, S.P. J. Biol. Chem. (2002) [Pubmed]
  27. A single amino acid substitution flanking the fourth calcium binding domain of alpha IIb prevents maturation of the alpha IIb beta 3 integrin complex. Wilcox, D.A., Wautier, J.L., Pidard, D., Newman, P.J. J. Biol. Chem. (1994) [Pubmed]
  28. Independent modulation of von Willebrand factor and fibrinogen binding to the platelet membrane glycoprotein IIb/IIIa complex as demonstrated by monoclonal antibody. Lombardo, V.T., Hodson, E., Roberts, J.R., Kunicki, T.J., Zimmerman, T.S., Ruggeri, Z.M. J. Clin. Invest. (1985) [Pubmed]
  29. A peptide corresponding to GPIIb alpha 300-312, a presumptive fibrinogen gamma-chain binding site on the platelet integrin GPIIb/IIIa, inhibits the adhesion of platelets to at least four adhesive ligands. Taylor, D.B., Gartner, T.K. J. Biol. Chem. (1992) [Pubmed]
  30. A novel homozygous mutation (1619delC) in GPIIb gene associated with Glanzmann thrombasthenia, the decay of GPIIb-mRNA and the synthesis of a truncated GPIIb unable to form complex with GPIIIa. Losonczy, G., Rosenberg, N., Kiss, C., Kappelmayer, J., Vereb, G., Kerényi, A., Balogh, I., Muszbek, L. Thromb. Haemost. (2005) [Pubmed]
  31. Molecular cloning and chemical synthesis of a region of platelet glycoprotein IIb involved in adhesive function. Loftus, J.C., Plow, E.F., Frelinger, A.L., D'Souza, S.E., Dixon, D., Lacy, J., Sorge, J., Ginsberg, M.H. Proc. Natl. Acad. Sci. U.S.A. (1987) [Pubmed]
  32. Extracellular signal-regulated kinase induces the megakaryocyte GPIIb/CD41 gene through MafB/Kreisler. Sevinsky, J.R., Whalen, A.M., Ahn, N.G. Mol. Cell. Biol. (2004) [Pubmed]
  33. Glycoprotein IIb/IIIa inhibition attenuates platelet-activating factor-induced platelet activation by reducing protein kinase C activity. Hu, H., Zhang, W., Li, N. J. Thromb. Haemost. (2003) [Pubmed]
  34. Megakaryocytic differentiation of HIMeg-1 cells induced by interferon gamma and tumour necrosis factor alpha but not by thrombopoietin. Li, J., Franco, R.S., Wang, Y., Pan, H.Q., Eaton, D., Cheng, T., Kaushansky, K., Dai, W. Cytokine (1998) [Pubmed]
  35. Thrombopoietin-induced expression of the glycoprotein IIb gene involves the transcription factor PU.1/Spi-1 in UT7-Mpl cells. Doubeikovski, A., Uzan, G., Doubeikovski, Z., Prandini, M.H., Porteu, F., Gisselbrecht, S., Dusanter-Fourt, I. J. Biol. Chem. (1997) [Pubmed]
  36. Beta2-integrins and acquired glycoprotein IIb/IIIa (GPIIb/IIIa) receptors cooperate in NF-kappaB activation of human neutrophils. Salanova, B., Choi, M., Rolle, S., Wellner, M., Luft, F.C., Kettritz, R. J. Biol. Chem. (2007) [Pubmed]
  37. Calcium-and integrin-binding protein regulates focal adhesion kinase activity during platelet spreading on immobilized fibrinogen. Naik, M.U., Naik, U.P. Blood (2003) [Pubmed]
  38. Epitope mapping by cDNA expression of a monoclonal antibody which inhibits the binding of von Willebrand factor to platelet glycoprotein IIb/IIIa. Piétu, G., Ribba, A.S., Chérel, G., Meyer, D. Biochem. J. (1992) [Pubmed]
  39. Study of platelet adhesion in patients with uncomplicated hypertension. Andrioli, G., Ortolani, R., Fontana, L., Gaino, S., Bellavite, P., Lechi, C., Minuz, P., Manzato, F., Tridente, G., Lechi, A. J. Hypertens. (1996) [Pubmed]
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