Skip to main content
PMC home page
The Journal of Cell Biology logoLink to The Journal of Cell Biology
. 1988 Apr 1;106(4):1359–1364. doi: 10.1083/jcb.106.4.1359

Glycoprotein Ic-IIa functions as an activation-independent fibronectin receptor on human platelets

PMCID: PMC2115005  PMID: 2966181

Abstract

Soluble fibronectin binds specifically to glycoprotein (GP) IIb-IIIa on thrombin-activated platelets, and this binding is not observed with platelets of patients with Glanzmann's thrombasthenia (GT) which lack GPIIb-IIIa. Here we report that GT platelets retain the ability to interact with fibronectin-coated surfaces. Adhesion to fibronectin does not require platelet activation and is inhibited by soluble fibronectin, antibodies specific for fibronectin, peptides containing the sequence Arg-Gly-Asp and polyclonal antibodies specific for band 3 of the chicken embryo fibroblast fibronectin receptor (anti-band 3). Using anti-band 3, we have purified a second fibronectin receptor from human platelets, a heterodimer composed of glycoproteins previously designated GPIc and GPIIa. The GPIc-IIa complex is found on both GT and normal platelets and appears to be identical to the GP138 kD-GP160 kD complex recently immunopurified by Giancotti et al. (1986. Exp. Cell Res. 163:47-62) and by Sonnenberg et al. (1987. J. Biol. Chem. 268:10376-10383). In this report, we provide the first evidence that GPIc-IIa actually mediates adhesion of platelets to fibronectin-coated surfaces. GPIc-IIa thus represents a second functional fibronectin receptor, distinct from GPIIb-IIIa, that is largely responsible for the adhesion of nonactivated platelets to fibronectin-coated surfaces.

Full Text

The Full Text of this article is available as a PDF (1.2 MB).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Akiyama S. K., Yamada S. S., Yamada K. M. Characterization of a 140-kD avian cell surface antigen as a fibronectin-binding molecule. J Cell Biol. 1986 Feb;102(2):442–448. doi: 10.1083/jcb.102.2.442. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Bennett J. S., Hoxie J. A., Leitman S. F., Vilaire G., Cines D. B. Inhibition of fibrinogen binding to stimulated human platelets by a monoclonal antibody. Proc Natl Acad Sci U S A. 1983 May;80(9):2417–2421. doi: 10.1073/pnas.80.9.2417. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Fitzgerald L. A., Steiner B., Rall S. C., Jr, Lo S. S., Phillips D. R. Protein sequence of endothelial glycoprotein IIIa derived from a cDNA clone. Identity with platelet glycoprotein IIIa and similarity to "integrin". J Biol Chem. 1987 Mar 25;262(9):3936–3939. [PubMed] [Google Scholar]
  4. Gardner J. M., Hynes R. O. Interaction of fibronectin with its receptor on platelets. Cell. 1985 Sep;42(2):439–448. doi: 10.1016/0092-8674(85)90101-1. [DOI] [PubMed] [Google Scholar]
  5. George J. N., Pickett E. B., Saucerman S., McEver R. P., Kunicki T. J., Kieffer N., Newman P. J. Platelet surface glycoproteins. Studies on resting and activated platelets and platelet membrane microparticles in normal subjects, and observations in patients during adult respiratory distress syndrome and cardiac surgery. J Clin Invest. 1986 Aug;78(2):340–348. doi: 10.1172/JCI112582. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Giancotti F. G., Comoglio P. M., Tarone G. A 135,000 molecular weight plasma membrane glycoprotein involved in fibronectin-mediated cell adhesion. Immunofluorescence localization in normal and RSV-transformed fibroblasts. Exp Cell Res. 1986 Mar;163(1):47–62. doi: 10.1016/0014-4827(86)90557-4. [DOI] [PubMed] [Google Scholar]
  7. Giancotti F. G., Languino L. R., Zanetti A., Peri G., Tarone G., Dejana E. Platelets express a membrane protein complex immunologically related to the fibroblast fibronectin receptor and distinct from GPIIb/IIIa. Blood. 1987 May;69(5):1535–1538. [PubMed] [Google Scholar]
  8. Grinnell F., Phan T. V. Platelet attachment and spreading on polystyrene surfaces: dependence on fibronectin and plasma concentration. Thromb Res. 1985 Jul 15;39(2):165–171. doi: 10.1016/0049-3848(85)90104-5. [DOI] [PubMed] [Google Scholar]
  9. Hasegawa T., Hasegawa E., Chen W. T., Yamada K. M. Characterization of a membrane-associated glycoprotein complex implicated in cell adhesion to fibronectin. J Cell Biochem. 1985;28(4):307–318. doi: 10.1002/jcb.240280409. [DOI] [PubMed] [Google Scholar]
  10. Hemler M. E., Huang C., Schwarz L. The VLA protein family. Characterization of five distinct cell surface heterodimers each with a common 130,000 molecular weight beta subunit. J Biol Chem. 1987 Mar 5;262(7):3300–3309. [PubMed] [Google Scholar]
  11. Horwitz A., Duggan K., Greggs R., Decker C., Buck C. The cell substrate attachment (CSAT) antigen has properties of a receptor for laminin and fibronectin. J Cell Biol. 1985 Dec;101(6):2134–2144. doi: 10.1083/jcb.101.6.2134. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Hynes R. O. Integrins: a family of cell surface receptors. Cell. 1987 Feb 27;48(4):549–554. doi: 10.1016/0092-8674(87)90233-9. [DOI] [PubMed] [Google Scholar]
  13. Ill C. R., Engvall E., Ruoslahti E. Adhesion of platelets to laminin in the absence of activation. J Cell Biol. 1984 Dec;99(6):2140–2145. doi: 10.1083/jcb.99.6.2140. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Kishimoto T. K., O'Connor K., Lee A., Roberts T. M., Springer T. A. Cloning of the beta subunit of the leukocyte adhesion proteins: homology to an extracellular matrix receptor defines a novel supergene family. Cell. 1987 Feb 27;48(4):681–690. doi: 10.1016/0092-8674(87)90246-7. [DOI] [PubMed] [Google Scholar]
  15. Kunicki T. J., Newman P. J. Synthesis of analogs of human platelet membrane glycoprotein IIb-IIIa complex by chicken peripheral blood thrombocytes. Proc Natl Acad Sci U S A. 1985 Nov;82(21):7319–7323. doi: 10.1073/pnas.82.21.7319. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Kunicki T. J., Nurden A. T., Pidard D., Russell N. R., Caen J. P. Characterization of human platelet glycoprotein antigens giving rise to individual immunoprecipitates in crossed-immunoelectrophoresis. Blood. 1981 Dec;58(6):1190–1197. [PubMed] [Google Scholar]
  17. Kunicki T. J., Pidard D., Rosa J. P., Nurden A. T. The formation of Ca++-dependent complexes of platelet membrane glycoproteins IIb and IIIa in solution as determined by crossed immunoelectrophoresis. Blood. 1981 Aug;58(2):268–278. [PubMed] [Google Scholar]
  18. Laemmli U. K. Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature. 1970 Aug 15;227(5259):680–685. doi: 10.1038/227680a0. [DOI] [PubMed] [Google Scholar]
  19. Lahav J., Hynes R. O. Involvement of fibronectin, Von Willebrand factor, and fibrinogen in platelet interaction with solid substrata. J Supramol Struct Cell Biochem. 1981;17(4):299–311. doi: 10.1002/jsscb.380170402. [DOI] [PubMed] [Google Scholar]
  20. Lawrence J. B., Gralnick H. R. Monoclonal antibodies to the glycoprotein IIb-IIIa epitopes involved in adhesive protein binding: effects on platelet spreading and ultrastructure on human arterial subendothelium. J Lab Clin Med. 1987 Apr;109(4):495–503. [PubMed] [Google Scholar]
  21. Leptin M. The fibronectin receptor family. Nature. 1986 Jun 19;321(6072):728–728. doi: 10.1038/321728a0. [DOI] [PubMed] [Google Scholar]
  22. Marguerie G. A., Plow E. F., Edgington T. S. Human platelets possess an inducible and saturable receptor specific for fibrinogen. J Biol Chem. 1979 Jun 25;254(12):5357–5363. [PubMed] [Google Scholar]
  23. Phillips D. R., Agin P. P. Platelet membrane defects in Glanzmann's thrombasthenia. Evidence for decreased amounts of two major glycoproteins. J Clin Invest. 1977 Sep;60(3):535–545. doi: 10.1172/JCI108805. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Phillips D. R., Agin P. P. Platelet plasma membrane glycoproteins. Evidence for the presence of nonequivalent disulfide bonds using nonreduced-reduced two-dimensional gel electrophoresis. J Biol Chem. 1977 Mar 25;252(6):2121–2126. [PubMed] [Google Scholar]
  25. Pidard D., Montgomery R. R., Bennett J. S., Kunicki T. J. Interaction of AP-2, a monoclonal antibody specific for the human platelet glycoprotein IIb-IIIa complex, with intact platelets. J Biol Chem. 1983 Oct 25;258(20):12582–12586. [PubMed] [Google Scholar]
  26. Plow E. F., Ginsberg M. H. Specific and saturable binding of plasma fibronectin to thrombin-stimulated human platelets. J Biol Chem. 1981 Sep 25;256(18):9477–9482. [PubMed] [Google Scholar]
  27. Plow E. F., McEver R. P., Coller B. S., Woods V. L., Jr, Marguerie G. A., Ginsberg M. H. Related binding mechanisms for fibrinogen, fibronectin, von Willebrand factor, and thrombospondin on thrombin-stimulated human platelets. Blood. 1985 Sep;66(3):724–727. [PubMed] [Google Scholar]
  28. Plow E. F., Pierschbacher M. D., Ruoslahti E., Marguerie G. A., Ginsberg M. H. The effect of Arg-Gly-Asp-containing peptides on fibrinogen and von Willebrand factor binding to platelets. Proc Natl Acad Sci U S A. 1985 Dec;82(23):8057–8061. doi: 10.1073/pnas.82.23.8057. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Pytela R., Pierschbacher M. D., Ginsberg M. H., Plow E. F., Ruoslahti E. Platelet membrane glycoprotein IIb/IIIa: member of a family of Arg-Gly-Asp--specific adhesion receptors. Science. 1986 Mar 28;231(4745):1559–1562. doi: 10.1126/science.2420006. [DOI] [PubMed] [Google Scholar]
  30. Pytela R., Pierschbacher M. D., Ruoslahti E. Identification and isolation of a 140 kd cell surface glycoprotein with properties expected of a fibronectin receptor. Cell. 1985 Jan;40(1):191–198. doi: 10.1016/0092-8674(85)90322-8. [DOI] [PubMed] [Google Scholar]
  31. Ruggeri Z. M., Bader R., de Marco L. Glanzmann thrombasthenia: deficient binding of von Willebrand factor to thrombin-stimulated platelets. Proc Natl Acad Sci U S A. 1982 Oct;79(19):6038–6041. doi: 10.1073/pnas.79.19.6038. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Sonnenberg A., Janssen H., Hogervorst F., Calafat J., Hilgers J. A complex of platelet glycoproteins Ic and IIa identified by a rat monoclonal antibody. J Biol Chem. 1987 Jul 25;262(21):10376–10383. [PubMed] [Google Scholar]
  33. Takada Y., Huang C., Hemler M. E. Fibronectin receptor structures in the VLA family of heterodimers. Nature. 1987 Apr 9;326(6113):607–609. doi: 10.1038/326607a0. [DOI] [PubMed] [Google Scholar]
  34. Takada Y., Strominger J. L., Hemler M. E. The very late antigen family of heterodimers is part of a superfamily of molecules involved in adhesion and embryogenesis. Proc Natl Acad Sci U S A. 1987 May;84(10):3239–3243. doi: 10.1073/pnas.84.10.3239. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from The Journal of Cell Biology are provided here courtesy of The Rockefeller University Press

RESOURCES