Studies on the Localization of Fibrinogen Binding Sites on Platelet Glycoprotein IIIa

  • Stefan Niewiarowski
  • Karin J. Norton
  • Jacquelynn J. Cook
  • Annette Eckardt
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 281)


The domains of various integrins involved in the binding to adhesive proteins are poorly characterized. The approaches to localize ligand binding sites on the adhesive receptors include studies on the genetic characterization of the defective β 2 subunits in leukocyte adhesion deficiency and the defective β 1 subunit in Glanzmann thrombasthenia, studies on the chemical and photoaffinity crosslinking of the adhesive ligands to the receptors, proteolytic degradation of the integrins, attempts to recognize binding sites with monoclonal antibodies, and studies on the synthetic peptides derived from glycoprotein IIIa (GPIIIa).


Human Platelet Platelet Membrane Leukocyte Adhesion Deficiency Fibrinogen Binding Vitronectin Receptor 
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  1. 1.
    E. I. B. Peerschke, The platelet fibrinogen receptor, Seminars in Hematology, 22:241–259 (1985).PubMedGoogle Scholar
  2. 2.
    D. R. Phillips, I. F. Charo, L. V. Parise, and L. A. Fitzgerald, The platelet membrane glycoprotein IIb-IIIa complex, Blood, 71:831–843 (1988).PubMedGoogle Scholar
  3. 3.
    R. O. Hynes, Integrins: A family of cell surface receptors, Cell, 48:549–554 (1987).PubMedCrossRefGoogle Scholar
  4. 4.
    E. F. Plow, J. C. Loftus, E. G. Levin, D. S. Fair, D. Dixon, J. Forsyth, and M. H. Ginsberg, Immunologic relationship between platelet membrane glycoprotein GPIIb/IIIa and cell surface molecules expressed by a variety of cells, Proc. Nat. Acad. Sci. (USA), 83:6002–6606 (1986).CrossRefGoogle Scholar
  5. 5.
    E. Ruoslahti and M. D. Pierschbacher, New perspectives in cell adhesion: RGD and Integrins, Science, (Wash., DC), 238:491–497 (1987).CrossRefGoogle Scholar
  6. 6.
    M. E. Hemler, C. Thang, and L. Schwarz, The VLA protein family. Characterization of five distinct cell surface heterodimers each with a common 130,000 molecular weight subunit, J. Biol. Chem., 262:3300–3309 (1987).PubMedGoogle Scholar
  7. 7.
    F. Sanchez-Madrid, J. A. Nagy, E. Robbins, P. Simm, and T. A. Springer, A human leukocyte differentiation antigen family with distinct alpha subunits and a common beta subunit: the lymphocyte-function associated antigen (LFA-1), the C3bi complement receptor (OKM1/MAC-1), and the p150, 95 molecule, J. Exp. Med.,158:1785–1803 (1983).PubMedCrossRefGoogle Scholar
  8. 8.
    J. C. Giltay, and J. A. van Mourik, Structure and function of endothelial cell integrins, Haemostasis, 18:376–389 (1988).PubMedGoogle Scholar
  9. 9.
    T. K. Kishimoto, K. O’Connor, and T. A. Springer, Leukocyte adhesion deficiency. Aberrant splicing of a conserved integrin sequence causes a moderate deficiency phenotype, J. Biol. Chem., 264:3588–3599 (1989).PubMedGoogle Scholar
  10. 10.
    J. A. Melero and J. Gonzalez-Rodriguez, Preparation of monoclonal antibodies against glycoprotein IIIa of human platelets: Their effect on platelet aggregation, Eur. J. Biochem., 141:421–427 (1984).PubMedCrossRefGoogle Scholar
  11. 11.
    J. J. Calvete, G. Rivas, M. Maurui, M. V. Alvarez, J. L. McGregor, C. L. Hew, and J. Gonzalez-Rodriguez, Tryptic digestion of human GPIIIa. Isolation and biochemical characterization of the 23 kDa N-terminal glycopeptide carrying the antigenic determinant for a monoclonal antibody (P37) which inhibits platelet aggregation, Biochem. J.,250:697–704 (1988).PubMedGoogle Scholar
  12. 12.
    S. E. D’Souza, M. H. Ginsberg, T. A. Burke, S. C. T. Lam, and E. F. Plow, Localization of an Arg-Gly-Asp recognition site within an integrin adhesion receptor, Science,242:91–93 (1988).PubMedCrossRefGoogle Scholar
  13. 13.
    J. W. Smith and D. A. Cheresh, The Arg-Gly-Asp binding domain of the vitronectin receptor. Photoaffinity crosslinking implicates amino acid residues 61–203 of the beta subunit, J. Biol. Chem., 263:18726–18731 (1988).PubMedGoogle Scholar
  14. 14.
    J. C. Loftus, T. E. O’Toole, E. F. Plow, and M. H. Ginsberg, Identification of a GPIIa-IIIa mutation in a glanzmanns variant associated with loss of RGD binding function, Blood, 74 (suppl 1), 58a (abstract) (1989).Google Scholar
  15. 15.
    S. E. D’Souza, M. H. Ginsberg, and E. F. Plow, Defining the ligand recognition site within the platelet adhesion receptor GPIIb-IIIa, Blood, 74 (suppl 1), 90a (abstract) (1989).Google Scholar
  16. 16.
    J. Greenberg, J. L. Or, M. A. Packham, M. A. Guccione, E. J. Harfenist, R. L. Kinlough-Rathbone, D. W. Perry, and J. F. Mustard, The effect of pretreatment of human or rabbit platelets with chymotrypsin on their responses to human fibrinogen and aggregating agents, Blood, 54:753–765 (1979).PubMedGoogle Scholar
  17. 17.
    S. Niewiarowski, A. Z. Budzynski, T. A. Morinelli, T. M. Brudzynski, and G. J. Steward, Exposure of fibrinogen receptor on human platelets by proteolytic enzymes, J. Biol. Chem.,256:917–925 (1981).PubMedGoogle Scholar
  18. 18.
    E. Kornecki, Y. H. Ehrlich, D. D. D. D. Demars, and R. H. Lenox, Exposure of fibrinogen receptors in human platelets by surface proteolysis with elastase, J. Clin. Invest, 77:750–756 (1986).PubMedCrossRefGoogle Scholar
  19. 19.
    E. Kornecki, Y. M. Ehrlich, R. Egbring, E. Gramse, R. Seitz, A. Eckardt, H. Lukasiewicz, and S. Niewiarowski, Granulocyte-platelet interactions and platelet fibrinogen receptor exposure, Amer. J. Physiol., 225:H651–H658 (1988).Google Scholar
  20. 20.
    E. G. Kornecki, G. P. Tuszynski, and S. Niewiarowski, Inhibition of fibrinogen receptor-mediated platelet aggregation by heterologous anti-human platelet membrane antibody: significance of an MR = 66,000 protein derived from glycoprotein IIIa, J. Biol. Chem., 285:9349–9356 (1983).Google Scholar
  21. 21.
    S. Niewiarowski, K. J. Norton, A. Eckardt, H. Lukasiewicz, J. C. Holt, and E. Kornecki, Structural and functional characterization of major platelet membrane components derived by limited proteolysis of glycoprotein IIIa, Biochim. Biophys. Acta, 983:91–99 (1989).PubMedCrossRefGoogle Scholar
  22. 22.
    L. A. Fitzgarld, B. Steiner, S. C. Rall, S. S. Jr., Lo, and D. R. Phillips, Protein sequence of endothelial glycoprotein IIIa derived from a cDNA clone, J. Biol. Chem., 262:3936–3939 (1987).Google Scholar
  23. 23.
    A. B. Zimrin, R. Eisman, G. F. Vilaire, E. Schwartz, J. S. Bennett, and M. Poncz, Structure of platelet glycoprotein IIIa. A common subunit for two different membrane receptors, J. Clin. Invest., 81:1470–1475 (1988).PubMedCrossRefGoogle Scholar
  24. 24.
    J. Beer and B. S. Coller, Evidence that platelet glycoprotein IIIa has a large disulfide bonded loop that is susceptible to proteolytic cleavage, J. Biol. Chem., 64:17564–17573 (1989).Google Scholar
  25. 25.
    S. K. A. Law, J. Gagnon, J. E. K. Hildreth, C. E. Wells, A. C. Willis, and A. J. Wong, The primary structure of the beta subunit of the cell surface adhesion glycoproteins LFA-1, CR3 and p150, 95 and its relationship to the fibronectin receptor, EMBO Journal, 6:915–919 (1987).PubMedGoogle Scholar
  26. 26.
    J. W. Tamkun, D. W. DeSimone, D. Fonda, R. S. Patel, C. Buck, A. F. Horwitz, and R. O. Hynes, Structure of integrin, a glycoprotein involved in the transmembrane linkage between fibronectin and actin, Cell,46:271–282.Google Scholar
  27. 27.
    K. J. Norton, J. J. Cook, and S. Niewiarowski, Effect of GPIIIa 217–232 on fibrinogen binding to human platelets, Blood,74:(suppl 1), 90a (abstract).Google Scholar
  28. 28.
    J. J. Cook, K. J. Norton, and S. Niewiarowski, Immunochemical characterization of GPIIIa 108–128 and GPIIIa 217–232, Blood, 74:(suppl 1), 92a (abstract).Google Scholar
  29. 29.
    K. J. Norton, “Structural and functional characterization of potential fibrinogen binding sites on glycoprotein IIIa of human platelets.” Dissertation submitted to the Department of Physiology, Temple University School of Medicine in partial fulfillment of the requirements for the degree of Doctor of Philosophy, Philadelphia, PA, pp. 139 (1989).Google Scholar
  30. 30.
    J. S. Bennett, J. A. Hoxie, S. F. Leitman, G. Vilaire, and D. B. Cines, Inhibition of fibrinogen binding to stimulated human platelets by a monoclonal antibody, Proc. Nat. Acad. Sci., (USA), 80:2417–2421 (1983).CrossRefGoogle Scholar
  31. 31.
    R. L. Nachman and L. L. K. Leung, Complex formation of platelet membrane glycoproteins IIb and IIIa with fibrinogen, J. Clin. Invest., 69:263–269 (1982).PubMedCrossRefGoogle Scholar
  32. 32.
    I. F. Charo, L. Nanninzi, D. R. Phillips, M. A. Hsu, and R. M. Scarborough, Inhibition of fibrinogen binding to GPIIb/IIIa by a GPIIIa peptide, Blood, 74:(suppl 1), 135a (abstract) (1989). Google Scholar

Copyright information

© Springer Science+Business Media New York 1990

Authors and Affiliations

  • Stefan Niewiarowski
    • 1
  • Karin J. Norton
    • 1
  • Jacquelynn J. Cook
    • 1
  • Annette Eckardt
    • 1
  1. 1.Department of Physiology and Thrombosis Research CenterTemple University School of MedicinePhiladelphiaUSA

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