Logo of jcellbiolHomeThe Rockefeller University PressEditorsContactInstructions for AuthorsThis issue
J Cell Biol. 1990 Dec 1; 111(6): 2795–2800.
PMCID: PMC2116382

The vitronectin receptor alpha v beta 3 binds fibronectin and acts in concert with alpha 5 beta 1 in promoting cellular attachment and spreading on fibronectin


The vitronectin receptor (alpha v beta 3) is a member of the integrin superfamily of adhesive protein receptors that mediate a wide spectrum of adhesive cellular interactions, including attachment to vitronectin, von Willebrand factor, fibrinogen, and thrombospondin. We have studied the binding of fibronectin to the purified vitronectin receptor, and the role of this receptor in the attachment of cells to fibronectin. A solid-phase microtiter assay was developed to investigate the binding properties of the vitronectin receptor. Purified alpha v beta 3 bound fibronectin with high affinity in a saturable, divalent cation- dependent manner. Binding was inhibited by soluble vitronectin, by RGD- containing peptides, and by LM609, a monoclonal antibody against the vitronectin receptor known to inhibit the binding of adhesive proteins to alpha v beta 3. Immunoinhibition experiments showed that M21 human melanoma cells, which express the fibronectin receptor, alpha 5 beta 1, as well as alpha v beta 3, used both of these integrins to attach and spread on fibronectin. In support of this finding, M21-L cells, a variant cell line that specifically lacks alpha v beta 3 but expresses alpha v beta 1, attached and spread poorly on fibronectin. In addition, alpha v beta 3 from surface-labeled M21 cells was retained, and selectively eluted by RGDS from a fibronectin affinity column. These results indicate that alpha v beta 3 acts in concert with alpha 5 beta 1 in promoting fibronectin recognition by these cells. We conclude that fibronectin binds to the alpha v beta 3 vitronectin receptor specifically and with high affinity, and that this interaction is biologically relevant in supporting cell adhesion to matrix proteins.

Full Text

The Full Text of this article is available as a PDF (1.1M).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.
  • Charo IF, Fitzgerald LA, Steiner B, Rall SC, Jr, Bekeart LS, Phillips DR. Platelet glycoproteins IIb and IIIa: evidence for a family of immunologically and structurally related glycoproteins in mammalian cells. Proc Natl Acad Sci U S A. 1986 Nov;83(21):8351–8355. [PMC free article] [PubMed]
  • Charo IF, Bekeart LS, Phillips DR. Platelet glycoprotein IIb-IIIa-like proteins mediate endothelial cell attachment to adhesive proteins and the extracellular matrix. J Biol Chem. 1987 Jul 25;262(21):9935–9938. [PubMed]
  • Cheresh DA. Human endothelial cells synthesize and express an Arg-Gly-Asp-directed adhesion receptor involved in attachment to fibrinogen and von Willebrand factor. Proc Natl Acad Sci U S A. 1987 Sep;84(18):6471–6475. [PMC free article] [PubMed]
  • Cheresh DA, Spiro RC. Biosynthetic and functional properties of an Arg-Gly-Asp-directed receptor involved in human melanoma cell attachment to vitronectin, fibrinogen, and von Willebrand factor. J Biol Chem. 1987 Dec 25;262(36):17703–17711. [PubMed]
  • Cheresh DA, Berliner SA, Vicente V, Ruggeri ZM. Recognition of distinct adhesive sites on fibrinogen by related integrins on platelets and endothelial cells. Cell. 1989 Sep 8;58(5):945–953. [PubMed]
  • Coller BS, Peerschke EI, Scudder LE, Sullivan CA. A murine monoclonal antibody that completely blocks the binding of fibrinogen to platelets produces a thrombasthenic-like state in normal platelets and binds to glycoproteins IIb and/or IIIa. J Clin Invest. 1983 Jul;72(1):325–338. [PMC free article] [PubMed]
  • Coller BS, Beer JH, Scudder LE, Steinberg MH. Collagen-platelet interactions: evidence for a direct interaction of collagen with platelet GPIa/IIa and an indirect interaction with platelet GPIIb/IIIa mediated by adhesive proteins. Blood. 1989 Jul;74(1):182–192. [PubMed]
  • Conforti G, Zanetti A, Pasquali-Ronchetti I, Quaglino D, Jr, Neyroz P, Dejana E. Modulation of vitronectin receptor binding by membrane lipid composition. J Biol Chem. 1990 Mar 5;265(7):4011–4019. [PubMed]
  • Duband JL, Nuckolls GH, Ishihara A, Hasegawa T, Yamada KM, Thiery JP, Jacobson K. Fibronectin receptor exhibits high lateral mobility in embryonic locomoting cells but is immobile in focal contacts and fibrillar streaks in stationary cells. J Cell Biol. 1988 Oct;107(4):1385–1396. [PMC free article] [PubMed]
  • D'Souza SE, Ginsberg MH, Burke TA, Plow EF. The ligand binding site of the platelet integrin receptor GPIIb-IIIa is proximal to the second calcium binding domain of its alpha subunit. J Biol Chem. 1990 Feb 25;265(6):3440–3446. [PubMed]
  • Elices MJ, Hemler ME. The human integrin VLA-2 is a collagen receptor on some cells and a collagen/laminin receptor on others. Proc Natl Acad Sci U S A. 1989 Dec;86(24):9906–9910. [PMC free article] [PubMed]
  • Engvall E, Ruoslahti E, Miller EJ. Affinity of fibronectin to collagens of different genetic types and to fibrinogen. J Exp Med. 1978 Jun 1;147(6):1584–1595. [PMC free article] [PubMed]
  • Humphries MJ, Olden K, Yamada KM. A synthetic peptide from fibronectin inhibits experimental metastasis of murine melanoma cells. Science. 1986 Jul 25;233(4762):467–470. [PubMed]
  • Hynes RO. Integrins: a family of cell surface receptors. Cell. 1987 Feb 27;48(4):549–554. [PubMed]
  • Kirchhofer D, Languino LR, Ruoslahti E, Pierschbacher MD. Alpha 2 beta 1 integrins from different cell types show different binding specificities. J Biol Chem. 1990 Jan 15;265(2):615–618. [PubMed]
  • Kloczewiak M, Timmons S, Lukas TJ, Hawiger J. Platelet receptor recognition site on human fibrinogen. Synthesis and structure-function relationship of peptides corresponding to the carboxy-terminal segment of the gamma chain. Biochemistry. 1984 Apr 10;23(8):1767–1774. [PubMed]
  • Lam SC, Plow EF, D'Souza SE, Cheresh DA, Frelinger AL, 3rd, Ginsberg MH. Isolation and characterization of a platelet membrane protein related to the vitronectin receptor. J Biol Chem. 1989 Mar 5;264(7):3742–3749. [PubMed]
  • Lawler J, Weinstein R, Hynes RO. Cell attachment to thrombospondin: the role of ARG-GLY-ASP, calcium, and integrin receptors. J Cell Biol. 1988 Dec;107(6 Pt 1):2351–2361. [PMC free article] [PubMed]
  • Phillips DR, Jennings LK, Edwards HH. Identification of membrane proteins mediating the interaction of human platelets. J Cell Biol. 1980 Jul;86(1):77–86. [PMC free article] [PubMed]
  • Pytela R, Pierschbacher MD, 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. [PubMed]
  • Pytela R, Pierschbacher MD, Ruoslahti E. A 125/115-kDa cell surface receptor specific for vitronectin interacts with the arginine-glycine-aspartic acid adhesion sequence derived from fibronectin. Proc Natl Acad Sci U S A. 1985 Sep;82(17):5766–5770. [PMC free article] [PubMed]
  • Pytela R, Pierschbacher MD, Ginsberg MH, Plow EF, 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. [PubMed]
  • Santoro SA. Identification of a 160,000 dalton platelet membrane protein that mediates the initial divalent cation-dependent adhesion of platelets to collagen. Cell. 1986 Sep 12;46(6):913–920. [PubMed]
  • Savill J, Dransfield I, Hogg N, Haslett C. Vitronectin receptor-mediated phagocytosis of cells undergoing apoptosis. Nature. 1990 Jan 11;343(6254):170–173. [PubMed]
  • Smith JW, Cheresh DA. The Arg-Gly-Asp binding domain of the vitronectin receptor. Photoaffinity cross-linking implicates amino acid residues 61-203 of the beta subunit. J Biol Chem. 1988 Dec 15;263(35):18726–18731. [PubMed]
  • Wayner EA, Garcia-Pardo A, Humphries MJ, McDonald JA, Carter WG. Identification and characterization of the T lymphocyte adhesion receptor for an alternative cell attachment domain (CS-1) in plasma fibronectin. J Cell Biol. 1989 Sep;109(3):1321–1330. [PMC free article] [PubMed]
  • Werb Z, Tremble PM, Behrendtsen O, Crowley E, Damsky CH. Signal transduction through the fibronectin receptor induces collagenase and stromelysin gene expression. J Cell Biol. 1989 Aug;109(2):877–889. [PMC free article] [PubMed]
  • Yatohgo T, Izumi M, Kashiwagi H, Hayashi M. Novel purification of vitronectin from human plasma by heparin affinity chromatography. Cell Struct Funct. 1988 Aug;13(4):281–292. [PubMed]

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


Save items

Related citations in PubMed

See reviews...See all...

Cited by other articles in PMC

See all...


  • Compound
    PubChem chemical compound records that cite the current articles. These references are taken from those provided on submitted PubChem chemical substance records. Multiple substance records may contribute to the PubChem compound record.
  • PubMed
    PubMed citations for these articles
  • Substance
    PubChem chemical substance records that cite the current articles. These references are taken from those provided on submitted PubChem chemical substance records.

Recent Activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...