Skip to main content
Log in

The vitronectin receptor (αVβ3) as an example for the role of integrins in T lymphocyte stimulation

  • Published:
Immunologic Research Aims and scope Submit manuscript

Abstract

Integrins are a family of cell surface receptors which mediate the adhesion of cells to each other or to extracellular matrix (ECM) proteins. The interaction of integrins with their ligands or counter-receptors was initially considered to be a one-way process in that cells actively regulate the interaction of integrins with their ligands (‘inside-out signal’). In contrast, it was not obvious that cells would receive a signal from the outside via the integrin heterodimers following ligand binding (‘outside-in signal’). Recent evidence increasingly supports the active role of integrins in cell activation and proliferation. Many reports describe the effects of integrin-mediated signaling in lymphoid cells. Our studies of γ/δ T cells, expressing the β3 integrin vitronectin receptor (VNR), reflect some of the consequences this active interaction between lymphocytes and the ECM could have for T cell activation and differentiation. The VNR has been described as a T cell costimulatory molecule. We recently reported that the VNR has the potential to stimulate cytokine secretion in T cell hybridomas without involvement of T cell receptor-mediated signals. Further studies demonstrated tyrosine phosphorylation of proteins following VNR cross-linking and the interaction of the VNR with protein kinases. Intensive research focuses on the signal transduction mechanisms of integrins and their interaction with other costimulatory or activation molecules. This knowledge is important to better understand the role of adhesion molecules, the ECM, and the cellular microenvironment for lymphocyte activation and differentation.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  1. Collins TL, Kassner PD, Bierer BE, Burakoff SJ: Adhesion receptors in lymphocyte activation. Curr Opin Immunol 1994;6:385–393.

    Article  PubMed  CAS  Google Scholar 

  2. Springer TA: Adhesion receptors of the immune system. Nature 1990; 346:425–434.

    Article  PubMed  CAS  Google Scholar 

  3. Roberts K, Yokoyama WM, Kehn PJ, Shevach EM: The vitronectin receptor sterves as an accessory molecule for the activation of a subset of γ/δ T cells. J Exp Med 1991;173: 231–240.

    Article  PubMed  CAS  Google Scholar 

  4. Wilde DB, Roberts K, Sturmhöfel K, Kikuchi G, Coligan JE, Shevach EM: Mouse autoreactive γ/δ T cells. I: Functional properties of autoreactive T cell hybridomas. Eur J Immunol 1992;22:483–489.

    Article  PubMed  CAS  Google Scholar 

  5. Rabinowich H, Lin W, Amoscato A, Herberman RB, Whiteside TL: Expression of vitronectin receptor on human NK cells and its role in protein phosphorylation, cytokine production, and cell proliferation. J Immunol 1995;154:1124–1135.

    PubMed  CAS  Google Scholar 

  6. Sturmhöfi K, Brando C, Martinon F, Shevach EM, Coligan JE: Antigen-independent, integrin-mediated T cell activation. J Immunol 1995; 154:2104–2111.

    Google Scholar 

  7. Yamada KM, Miyamoto S: Integrin transmembrane signaling and cytoskeletal control. Curr Opin Cell Biol 1995;7:681–689.

    Article  PubMed  CAS  Google Scholar 

  8. Stewart M, Thiel M, Hogg N: Leukocyte integrins. Curr Opin Cell Biol 1995;7:690–696.

    Article  PubMed  CAS  Google Scholar 

  9. Carreno M, Gresham HD, Brown EJ: Isolation of leukocyte response integrin: A novel RGD-binding protein involved in regulation of phagocytic function. Clin Immunol Immunopathol 1993;69:43–51.

    Article  PubMed  CAS  Google Scholar 

  10. Elices MJ, Osborn L, Takada Y, Crouse C, Luhowsky S, Hemler ME, Lobb RR: VCAM-1 on activated endothelium interacts with the leukocyte integrin VLA-4 at a site distinct from the VLA-4/fibronectin binding site. Cell 1990;60:577–584.

    Article  PubMed  CAS  Google Scholar 

  11. Hemler ME: VLA proteins in the integrin family: Structures, functions, and their role on leukocytes. Annu Rev Immunol 1990;8:365–400.

    Article  PubMed  CAS  Google Scholar 

  12. Wadsworth S, Halvorson MJ, Coligan JE: Developmentally regulated expression of the β4 integrin on immature mouse thymocytes. J Immunol 1992;149:421–428.

    PubMed  CAS  Google Scholar 

  13. Heino J, Ignotz RA, Hemler ME, Crouse C, Massagué J: Regulation of cell adhesion receptors by transforming growth factor-β: Concomitant regulation of integrins that share a common β1 subunit. J Biol Chem 1989;264:380–388

    PubMed  CAS  Google Scholar 

  14. Piela TH, Korn JH: Lymphocyte-fibroblast adhesion induced by interferon-γ. Cell Immunol 1988;114: 149–160.

    Article  PubMed  CAS  Google Scholar 

  15. Wilkins JA, Stupack D, Stewart S, Caixia S: β1 integrin-mediated lymphocyte adherence to extracellular matrix is enhanced by phorbol ester treatment. Eur J Immunol 1991;21: 517–522.

    Article  PubMed  CAS  Google Scholar 

  16. Ignotz RA, Heino J, Massagué J: Regulation of cell adhesion receptors by transforming growth factor-β: Regulation of vitronectin receptor and LFA-1. J Biol Chem 1989;264: 389–392.

    PubMed  CAS  Google Scholar 

  17. Kitazawa S, Ross FP, McHugh K, Teitelbaum SL: Interleukin-4 induces expression of the integrin αVβ3 via transactivation of the β3 gene. J Biol Chem 1995;270:4115–4120.

    Article  PubMed  CAS  Google Scholar 

  18. Huang S, Endo RI, Nemerow GR: Upregulation of integrins αvβ3 and αvβ5 on human monocytes and T lymphocytes facilitates adenovirus-mediated gene delivery. J Virol 1995;69:2257–2263.

    PubMed  CAS  Google Scholar 

  19. Dedhar S, Robertson K, Gray V: Induction of expression of the αvβ3 integrin heterodimers during retinoic acid-induced neuronal differentiation of murine embryonal carcinoma cells. J Biol Chem 1991;266: 21846–21852.

    PubMed  CAS  Google Scholar 

  20. Felding-Habermann B, Cheresh DA: Vitronectin and its receptors, Curr Opin Cell Biol 1993;5:864–868.

    Article  PubMed  CAS  Google Scholar 

  21. Klingemann H, Dedhar S: Distribution of integrins on human peripheral blood mononuclear cells. Blood 1989;74:1348–1354.

    PubMed  CAS  Google Scholar 

  22. Mäenpää A, Jääskeläinen J, Carpén O, Patarroyo M, Timonen T: Expression of integrins and other adhesion molecules on NK cells: Impact of IL-2 on short- and long-term cultures. Int J Cancer 1993;83:850–855.

    Article  Google Scholar 

  23. Maxfield SR, Moulder K, Koning F, Elbe A, Stingl G, Coligan JE, Shevach EM, Yokoyama WM: Murine T cells express a cell surface receptor for multiple extracellular matrix proteins. J Exp Med 1989;169: 2173–2190.

    Article  PubMed  CAS  Google Scholar 

  24. Takahashi K, Nakamura T, Koyanagi M, Kato K, Hashimoto Y, Yagita H, Okumura K: A murine very late activation antigen-like extracellular matrix receptor involved in CD2+ and lymphocyte function-associated antigen-1-independent killer-target cell interaction. J Immunol 1990;145:4371–4379.

    PubMed  CAS  Google Scholar 

  25. Stupack DG, Shen C, Wilkins JA: Induction of ανβ3 integrin-mediated attachment to extracellular matrix in β1} integrin (CD29)-negative B cell lines. Exp Cell Res 1992;203:443–448.

    Article  PubMed  CAS  Google Scholar 

  26. Dustin ML, Springer TA: T-cell receptor cross-linking transiently stimulates adhesiveness through LFA-1. Nature 1989;341:619–624.

    Article  PubMed  CAS  Google Scholar 

  27. Tanaka Y, Albeida SM, Horgan KJ, van Seventer GA, Shimizu Y, Newman W, Hallam J, Newman PJ, Buck CA, Shaw S: CD31 expressed on distinctive T cell subsets is a preferential amplifier of β1 integrin-mediated adhesion. J Exp Med 1992; 176:245–253.

    Article  PubMed  CAS  Google Scholar 

  28. Bianchine PJ, Burd PR, Metcalfe DD: IL-3-dependent mast cells attach to plate-bound vitronectin: Demonstration of augmented proliferation in response to signals transduced via cell surface vitronectin receptors. J Immunol 1992;149:3665–3671.

    PubMed  CAS  Google Scholar 

  29. Groux H, Haet S, Valentin H, Pham D, Bernard A: Suppressor effects and cyclic AMP accumulation by the CD29 molecule of CD4+ lymphocytes. Nature 1989;339:152.

    Article  PubMed  CAS  Google Scholar 

  30. McNamee HP, Ingber DE, Schwartz MA: Adhesion to fibronectin stimulates inositol lipid synthesis and enhances PDGF-induced inositol lipid breakdown. J Cell Biol 1993;121: 673.

    Article  PubMed  CAS  Google Scholar 

  31. Schwartz MA, Lechene C, Ingber DE: Insoluble fibronectin activated the Na/H antiporter by clustering and immobilizing integrin αβ, independent of cell shape. Proc Natl Acad Sci USA 1991;88:7849

    Article  PubMed  CAS  Google Scholar 

  32. Schwartz MA: Spreading of human endothelial cells on fibronectin or vitronectin triggers elevation of intracellular free calcium. J Cell Biol 1993;120:1003–1010.

    Article  PubMed  CAS  Google Scholar 

  33. Juliano RL, Varner JA: Adhesion molecules in cancer: The role of integrins. Curr Opin Cell Biol 1993;5: 812–818.

    Article  PubMed  CAS  Google Scholar 

  34. Pacifici R, Roman J, Kimble R, Civitelli R, Brownfield CM, Bizzarri C: Ligand binding to monocyte α5β1 integrin activated the α2β1 receptor via the α5 subunit cytoplasmic domain and protein kinase C. J Immunol 1994;153:2222–2233.

    PubMed  CAS  Google Scholar 

  35. Blystone SD, Graham IL, Lindberg FP, Brown EJ: Integrin ανα3 differentially regulated adhesive and phagocytic functions of the fibronectin receptor α5β1. J Cell Biol 1994; 127:1129–1137.

    Article  PubMed  CAS  Google Scholar 

  36. van Noesel C, Miedema F, Brouwer M, de Rie MA, Aarden LA, van Lier RA: Regulatory properties of LFA-1 a and b chains in human T-lymphocyte activation. Nature 1988;333: 850–852.

    Article  PubMed  Google Scholar 

  37. van Seventer GA, Shimizu Y, Horgan KJ, Shaw S: The LFA-1 ligand ICAM-1 provides an important costimulatory signal for T cell receptor-mediated activation of resting T cells. J Immunol 1990;144:4579–4586.

    PubMed  Google Scholar 

  38. Damle NK, Klussman K, Linsley PS, Aruffo A, Ledbetter JA: Differential regulatory effects of intercellular adhesion molecule-1 on costimulation by the cd28 counter-receptor b7. J Immunol 1992;149:2541–2548.

    PubMed  CAS  Google Scholar 

  39. Hernandez-Caselles T, Rubio G, Campanero MR, Angel del Pozo M, Muro M, Sanchez-Madrid F, Apariclo P: ICAM-3, the third LFA-1 counterreceptor, is a co-stimulatory molecule for both resting and activated T lymphocytes. Eur J Immunol 1993;23:2799–2806.

    Article  PubMed  CAS  Google Scholar 

  40. Matsuyama T, Yamada A, Kay J, Yamada KM, Akiyama SK, Schlossman SF, Morimoto C: Activation of CD4 cells by fibronectin and anti-CD3 antibody: A synergistic effect mediated by the VLA-5 fibronectin receptor complex. J Exp Med 1989; 170:1133–1148.

    Article  PubMed  CAS  Google Scholar 

  41. Shimizu Y, van Seventer GA, Horgan KJ, Shaw S: Costimulation of proliferative responses of resting CD4+ T cells by the interaction of VLA-4 and VLA-5 with fibronectin or VLA-6 with laminin. J Immunol 1990;145:59–67.

    PubMed  CAS  Google Scholar 

  42. Burkly LC, Jakubowski A, Newman BM, Rosa MD, Chi-Rosso G, Lobb RR: Signaling by vascular cell adhesion molecule-1 (VCAM-1) through VLA-4 promotes CD3-dependent T cell proliferation. Eur J Immunol 1991;21: 2871–2875.

    Article  PubMed  CAS  Google Scholar 

  43. Utsumi K, Swada M, Narumiya S, Nagamine J, Sakata T, Iwagami S, Kita Y, Teraoka H, Hirano H, Ogata M, Hamaoka T, Fujiwara H: Adhesion of immature thymocytes to thymic stromal cells through fibronectin molecules and its significance for the induction of thymocyte differentiation. Proc Natl Acad Sci USA 1991;88:5685–5689.

    Article  PubMed  CAS  Google Scholar 

  44. Moulder K, Roberts K, Shevach EM, Coligan JE: The mouse vitronectin receptor is a T cell activation antigen. J Exp Med 1991;173:343–347.

    Article  PubMed  CAS  Google Scholar 

  45. Ezquerra A, Wilde DB, McConnell TJ, Sturmhöfel K, Valas RB, Shevach EM, Coligan JE: Mouse autoreactive γ/δ T cells. II: Molecular characterization of the T cell receptor. Eur J Immunol 1992;22:491–498.

    Article  PubMed  CAS  Google Scholar 

  46. Kikuchi GE, Roberts K, Shevach EM, Coligan JE: Gene transfer demonstrates that the Vγ1.1Cγ4Vδ6Cδ T cell receptor is essential for autoreactivity. J Immunol 1992;148: 1302–1307.

    PubMed  CAS  Google Scholar 

  47. O'Brien RL, Fu Y, Cranfill R, Dallas A, Ellis C, Reardon C, Lang J, Carding SR, Kubo R, Born W: Heat shock protein Hsp60-reactive γδ cells: A large, diversified T-lymphocyte subset with highly focused specificity. Proc Natl Acad Sci USA 1992;89:4348–4352.

    Article  PubMed  Google Scholar 

  48. Kaufmann SHE, Kabelitz D: Gamma/delta T lymphocytes and heat shock proteins. Curr Top Microbiol Immunol 1991;167:191–207.

    PubMed  CAS  Google Scholar 

  49. Takahashi K, Dai LC, Fuerst TR, Biddison WE, Earl PL, Moss B, Ennis FA: Specific lysis of human immunodeficiency virus type 1-infected cells by a HLA-A3.1-restricted CD8+ cytotoxic T-lymphocyte clone that recognizes a conserved peptide sequence within the gp41 subunit of the envelope protein. Proc Natl Acad Sci USA 1991; 88:10277–10281.

    Article  PubMed  CAS  Google Scholar 

  50. Maguire JE, van Seventer GA: Adhesion molecules as signal transducers in T-cell activation; in Shimizu Y (ed). Lymphocyte Adhesion Molecules, Austin, Candes, 1993, pp 313–332.

    Google Scholar 

  51. June CH, Ledbetter JA, Gillespie MM: T-cell proliferation involving the CD28 pathway is associated with cyclosporine-resistant interleukin 2 gene expression. Mol Cell Biol 1987;7:4472–4482.

    PubMed  CAS  Google Scholar 

  52. Meuer SC, Hussey RE, Fabbi M: An alternative pathway of T-cell activation: A functional role for the 50kd T11 sheep erythrocyte receptor protein. Cell 1984;36:897–906.

    Article  PubMed  CAS  Google Scholar 

  53. Brando C, Shevach EM: Engagement of the vitronectin receptor (ανβ3) on murine T cells stimulates tyrosine phosphorylation of a 115-kD protein. J Immunol 1995;154: 2005–2011.

    PubMed  CAS  Google Scholar 

  54. Letourneur F, Klausner RD: T-cell and basophil activation through the cytoplasmic tail of T-cell-receptor zeta family proteins. Proc Natl Acad Sci USA 1991;88:8905–8909.

    Article  PubMed  CAS  Google Scholar 

  55. Raulet DH: Antigens for γ/δ T cells. Nature 1989;339:342–343.

    Article  PubMed  CAS  Google Scholar 

  56. Huang MM, Lipfert L, Cunningham M, Brugge JS, Ginsberg MH, Shattil SJ: Adhesive ligand binding to integrin α11bβ3 stimulates tyrosine phosphorylation of novel protein substrates before phosphorylation of pp125FAK. J Cell Biol 1993;122: 473–483.

    Article  PubMed  CAS  Google Scholar 

  57. Kornberg LJ, Earp HS, Turner CE, Prockop C, Juliano RL: Signal transduction by integrins: Increased protein tyrosine phosphorylation caused by clustering of β1 integrins. Proc Natl Acad Sci USA 1991;88: 8392–8396.

    Article  PubMed  CAS  Google Scholar 

  58. Freedman A, Rhynhart K, Nojima Y, Svahn J, Eliseo L, Benjamin CD, Morimoto C, Vivier E: Stimulation of protein tyrosine phosphorylation in human B cells after ligation of the β1 integrin VLA-4. J Immunol 1993;150:1645–1652.

    PubMed  CAS  Google Scholar 

  59. Hamawy MM, Mergenhagen SE, Siraganian RP: Cell adherence to fibronectin and the aggregation of the high affinity immunoglobulin E receptor synergistically regulate tyrosine phosphorylation of 105–115-kDa proteins. J Biol Chem 1993; 268:5227–5233.

    PubMed  CAS  Google Scholar 

  60. Nojima Y, Rothstein DM, Sugita K, Schlossman SF, Morimoto C: Ligation of VLA-4 on T cells stimulates tyrosine phosphorylation of a 105-kD protein. J Exp Med 1992;175: 1045–1053.

    Article  PubMed  CAS  Google Scholar 

  61. Guan JL, Shalloway D: Regulation of focal adhesion-associated protein tyrosine kinase by both cellular adhesion and oncogenic transformation. Nature 1992;358:690–692.

    Article  PubMed  CAS  Google Scholar 

  62. Hanks SK, Calalb MB, Harpper MC, Patel SK: Focal adhesion protein-tyrosine kinase phosphorylated in response to cell attachment to fibronectin. Proc Natl Acad Sci USA 1992;89:8487–8491.

    Article  PubMed  CAS  Google Scholar 

  63. Nojima Y, Tachibana K, Sato T, Schlossman SF, Morimoto C: Focal adhesion kinase (pp125FAK) is tyrosine phosphorylated after engagement of α4β1 and α5β1 integrins on human T-lymphoblastic cells. Cell Immunol 1995;161:8–13.

    Article  PubMed  CAS  Google Scholar 

  64. Schaller MD, Borgman CA, Cobb BS, Vines RR, Reynolds AB, Parsons JT: pp125FAK, a structurally distinctive protein-tyrosine kinase associated with focal adhesions. Proc Natl Acad Sci USA 1992;89: 5192–5196.

    Article  PubMed  CAS  Google Scholar 

  65. Turner CE, Schaller MD, Parsons JT: Tyrosine phosphorylation of the focal adhesion kinase pp125FAK during development: Relation to paxillin. J Cell Sci 1993;105:637–645.

    PubMed  CAS  Google Scholar 

  66. Bockholt SM, Burridge K: Cell spreading on extracellular matrix proteins induces tyrosine phosphorylation of tensin. J Biol Chem 1993; 268:14565–14567.

    PubMed  CAS  Google Scholar 

  67. Tamkun JW, De Simone DW, Fonda D, Patel RS, Buck C, Horwitz AF, Hynes RO: Structure of integrin, a glycoprotein involved in the transmembrane linkage between fibronectin and actin. Cell 1986;46: 271–282.

    Article  PubMed  CAS  Google Scholar 

  68. Songyang Z, Margolis B, Chaudhuri M, Shoelson SE, Cantley LC: The phosphotyrosine interaction domain of SHC recognizes tyrosine-phosphorylated NPXY motif. J Biol Chem 1995;270:14863–14866.

    Article  PubMed  CAS  Google Scholar 

  69. Schaller MD, Otey CA, Hildebrand JD, Parsons JT: Focal adhesion kinase and paxillin bind to peptides mimicking β integrin cytoplasmic domains. J Cell Biol 1995;130: 1181–1187.

    Article  PubMed  CAS  Google Scholar 

  70. Klausner RD, Samelson LE: T cell antigen receptor activation pathways: The tyrosine kinase connection. Cell 1991;64:875–878.

    Article  PubMed  CAS  Google Scholar 

  71. Carmo AM, Mason DW, Beyers AD: Physical association of the cytoplasmic domain of CD2 with the tyrosine kinases p56les and p59fyn. Eur J Immunol 1993;23:2186–2201.

    Article  Google Scholar 

  72. Oda A, Druker BJ, Smith M, Salzman EW: Association of pp60src with Triton X-100-insoluble residue in human blood platelets requires platelet aggregation and actin polymerization. J Biol Chem 1992;267: 20075–20081 [erratum in J Biol Chem 1993; 268: 5339].

    PubMed  CAS  Google Scholar 

  73. Otey CA, Vasquez GB, Burridge K, Erickson BW: Mapping of the alpha-actinin binding site within the beta 1 integrin cytoplasmic domain. J Biol Chem 1993;268:21193–21197.

    PubMed  CAS  Google Scholar 

  74. Horwitz A, Duggan K, Buck C, Beckerle MC, Burridge K: Interaction of plasma membrane fibronectin receptor with talin—A transmembrane linkage. Nature 1986; 320:531–533.

    Article  PubMed  CAS  Google Scholar 

  75. Ingber DE, Dike L, Hansen L, Karp S, Liley H, Maniotis A, McNamee H, Mooney D, Plopper G, Sims J, Wang N: Cellular tensegrity: Exploring how mechanical changes in the cytoskeleton regulate cell growth, migration, and tissue pattern during morphogenesis. Int Rev Cytol 1994; 150:173–224.

    Article  PubMed  CAS  Google Scholar 

  76. Singhvi R, Kumar A, Lopez GP, Stephanopoulos GN, Wang DI, Whitesides GM, Ingber DE: Engineering cell shape and function. Science 1994;264:696–698.

    Article  PubMed  CAS  Google Scholar 

  77. Lindberg FP, Gresham HD, Schwarz E, Brown EJ: Molecular cloning of integrin-associated protein: An immunoglobulin family member with multiple membrane-spanning domains implicated in ανβ3 ligand binding. J Cell Biol 1993;123:485–496.

    Article  PubMed  CAS  Google Scholar 

  78. Ticchioni M, Deckert M, Calandra D, Bernard G, Brown EJ, Bernard A: Integrin-associated protein (IAP, CD47) is involved in costimulation of human T lymphocytes (abstract). 9th Int Congr Immunol 1995, p 537.

  79. Cobb BS, Schalier MD, Leu TH, Parsons JT: Stable association of pp60src and pp59fyn with the focal adhesion-associated protein tyrosine kinase, pp125FAK. Mol Cell Biol 1994;14:147–155.

    PubMed  CAS  Google Scholar 

  80. Schlaepfer DD, Hanks SK, Hunter T, van der Geer P: Integrin-mediated signal transduction linked to Ras pathway by GRB2 binding to focal adhesion kinase. Nature 1994; 372: 786–791.

    PubMed  CAS  Google Scholar 

  81. Kharbanda S, Saleem A, Yuan Z, Emoto Y, Prasad KV, Kufe D: Stimulation of human monocytes with macrophage colony-stimulating factor induces a grb2-mediated association of the focal adhesion kinase pp125fak and dynamin. Proc Natl Acad Sci USA 1995;92:6132–6136.

    Article  PubMed  CAS  Google Scholar 

  82. Chen Q, Kinch MS, Lin TH, Burridge K, Juliano RL: Integrin-mediated cell adhesion activates mitogen-activated protein kinases. J Biol Chem 1994;269:26602–26605.

    PubMed  CAS  Google Scholar 

  83. Juliano RL, Haskill S: Signal transduction from the extracellular matrix. J Cell Biol 1993;120:577–584.

    Article  PubMed  CAS  Google Scholar 

  84. Clark EA, Brugge JS: Integrins and signal transduction pathways: The road taken. Science 1995;268:233–239.

    Article  PubMed  CAS  Google Scholar 

  85. Fan S, Brian AA, Lolla BA, Mackman N, Shen NL, Edgington TS: CD11a/CD18 (LFA-1) integrin engagement enhances biosynthesis of early cytokines by activated T cells. Cell Immunol 1993;148:48–59.

    Article  PubMed  CAS  Google Scholar 

  86. Yamada A, Nikaido T, Nojima Y, Schlossman S, Morimoto C: Activation of human CD4 T lymphocytes: Interaction of fibronection with VLA-5 receptor on CD4 cells induces the AP-1 transcription factor. J Immunol 1991;16:53–56.

    Google Scholar 

  87. Haskill S, Beg AA, Tompkins SM, Morris JS, Yurochko AD, Sampson-Johannes A, Mondal K, Ralph P, Baldwin AS: Characterization of an immediate-early gene induced in adherent monocytes that encodes IkappaB-like activity. Cell 1991;65: 1281–1289.

    Article  PubMed  CAS  Google Scholar 

  88. Guadagno TM, Ohtsubo M, Roberts JM, Assoian RK: A link between cyclin a expression and adhesion-dependent cell cycle progression. Science 1993;262:1572–1575 [erratum in Science 1994;263:455].

    Article  PubMed  CAS  Google Scholar 

  89. Meredith J, Takada Y, Formaro M, Languino LR, Schwartz MA: Inhibition of cell cycle progression by the alternatively spliced integrin beta(1C). Science 1995;269:1570–1572.

    Article  PubMed  CAS  Google Scholar 

  90. Sobel RA, Chen M, Maeda A, Hinojoza JR: Vitronectin and integrin vitronectin receptor localization in multiple sclerosis lesions. J Neuropathol Exp Neurol 1995;54:202–213.

    Article  PubMed  CAS  Google Scholar 

  91. Ashton BA, Ashton IK, Marshall MJ, Butler RC: Localisation of vitronectin receptor immunoreactivity and tartrate resistant acid phosphatase activity in synovium from patients with inflammatory or degenerative arthritis. Ann Rheum Dis 1993;52:133–137.

    PubMed  CAS  Google Scholar 

  92. Montgomery AMP, Reisfeld RA, Cheresh DA: Integrin ανβ3 rescues melanoma cells from apoptosis in three-dimensional dermal collagen. Proc Natl Acad Sci USA 1994;91: 8856–8860.

    Article  PubMed  CAS  Google Scholar 

  93. Felding-Habermann B, Mueller BM, Rohmerdahl CA, Cheresh DA: Involvement of integrin av gene expression in human melanoma tumorigenicity. J Clin Invest 1992;89: 2018–2022.

    Article  PubMed  CAS  Google Scholar 

  94. Seftor REB, Seftor EA, Gehlsen KR, Stetler-Sevenson WG, Brown PD, Ruoslahti E, Hendrix MJC: Role of the ανβ3 integrin in human melanoma cell invasion. Proc Natl Acad Sci USA 1992;89:1557–1561.

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Halvorson, M.J., Coligan, J.E. & Sturmhöfel, K. The vitronectin receptor (αVβ3) as an example for the role of integrins in T lymphocyte stimulation. Immunol Res 15, 16–29 (1996). https://doi.org/10.1007/BF02918281

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF02918281

Key Words

Navigation