Role of Integrin αvβ3 in Vascular Biology

Tatiana V. Byzova; Ramin Rabbani; Stanley E. D’Souza; Edward F. Plow

doi:10.1055/s-0037-1615250

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 1998; 80(05): 726-734
DOI: 10.1055/s-0037-1615250

Review Article

Schattauer GmbH

Role of Integrin α_vβ₃ in Vascular Biology

Authors

Tatiana V. Byzova

¹From the Joseph J. Jacobs Center for Thrombosis and Vascular Biology, The Cleveland Clinic Foundation, Cleveland, USA
Ramin Rabbani

¹From the Joseph J. Jacobs Center for Thrombosis and Vascular Biology, The Cleveland Clinic Foundation, Cleveland, USA
Stanley E. D’Souza

¹From the Joseph J. Jacobs Center for Thrombosis and Vascular Biology, The Cleveland Clinic Foundation, Cleveland, USA
Edward F. Plow

¹From the Joseph J. Jacobs Center for Thrombosis and Vascular Biology, The Cleveland Clinic Foundation, Cleveland, USA

Abstract

Introduction

A defining characteristic of vascular cells is their adhesive status. The predominant cells of the blood vessel, endothelial cells (EC) and smooth muscle cells (SMC), are normally adherent but can be induced to migrate in response to vascular injury and angiogenic stimuli. The circulating blood cells are ordinarily nonadhesive but can rapidly acquire an adhesive phenotype in response to physiologic and pathophysiologic stimuli. As prime examples, platelets become adherent to the subendothelial matrix and to one another during thrombus formation, and leukocytes first adhere to EC and then transmigrate during the inflammatory response. At a molecular level, the adhesive properties of the vascular cells are determined by the adhesion receptors on their cell-surface and the functional state of these receptors. To match the variety of requisite cellular adhesive reactions, the repertoire of adhesion receptors expressed by vascular cells is broad. Multiple representatives of the immunoglobulin-like, the selectin, the cadherin and the integrin families of adhesion receptors are present on and have been implicated in the functions of the vascular cells. The importance of these adhesion receptors in vascular cell function is underscored by the severe pathogenetic consequences of their congenital deficiencies, such as in Glanzmann’s thrombasthenia, LAD (Leucocyte Adhesion deficiency) I and LAD II (1-3).

The integrins are the largest and most broadly distributed of the families of cellular adhesion receptors. Of the integrins, α_vβ₃, originally identified as the vitronectin receptor, is particularly widely distributed. It is expressed at variable density on many types of vascular cells. Obviously, the adhesive properties of a cell are determined by its full repertoire of adhesion receptors. As an example, the adhesion of EC to fibrinogen/fibrin is mediated by no fewer than five receptors. Nevertheless, it is possible to dissect out the contributions of individual adhesion receptors, and α_vβ₃ has been implicated in many functional responses of vascular cells. This review focusses upon the role of α_vβ₃ in vascular cell biology. Other contributions of this multifunctional receptor, such as its role in neoplastic growth and invasion and in osteoclast-mediated bone resorption, are beyond the scope of this article and have been reviewed elsewhere (4, 5).

Full Text

References

References
1 George JN, Caen JP, Nurden AT. Glanzmann’s thrombasthenia: the spectrum of clinical disease. Blood 1990; 75: 1383-95.
2 Dana N, Clayton LK, Tennen DG, Pierce MW, Lachmann PJ, Law SA, Arnaout MA. Leukocytes from four patients with complete or partial leuCAM deficiency contain the common β-subunit precursor and β-subunit messenger RNA. J Clin Invest 1987; 79: 1010-5.
3 Von Andrian UH, Berger EM, Ramezani L, Chambers JD, Ochs HD, Harlan JM, Paulson JC, Etzioni A, Arfors K-E. In vivo behavior of neutrophils from two patients with distinct inherited leukocyte adhesion deficiency syndromes. J Clin Invest 1993; 91: 2893-7.
4 Dresner-Pollack R, Rosenblatt M. Blockade of osteoclast-mediated bone resorption through occupancy of the integrin receptor: a potential approach to the therapy of osteoporsis. J Cell Biochem 1994; 56: 323-30.
5 Nip J, Brodt P. The role of the integrin vitronectin receptor, α_vβ₃, in melanoma metastasis. Cancer Metastasis Rev 1995; 14: 241-52.
6 Cheresh DA. Human endothelial cells synthesize and express an Arg-GlyAsp-directed adhesion receptor involved in attachment to fibrinogen and von Willebrand factor. Proc Natl Acad Sci USA 1987; 84: 6471-5.
7 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; 262: 9935-8.
8 Dejana E, Languino LR, Colella S, Corbascio GC, Plow E, Ginsberg M, Marchisio PC. The localization of a platelet Gp IIb-IIIa-related protein in endothelial cell adhesion structures. Blood 1988; 71: 566-72.
9 Conforti G, Dominguez-Jimenez C, Zanetti A, Gimbrone Jr. MA, Cremona O, Marchisio PC, Dejana E. Human endothelial cells express integrin receptors on the luminal aspect of their membrane. Blood 1992; 80: 437-46.
10 Lampugnani MG, Resnati M, Dejana E, Marchisio PC. The role of inte-grins in the maintenance of endothelial monolayer integrity. J Cell Biol 1991; 112: 479-90.
11 Glass WF, II, Kreisberg JI. Regulation of integrin-mediated adhesion at focal contacts by cyclic AMP. J Cell Physiol 1993; 157: 296-306.
12 Swerlick RB, Brown EJ, Xu Y, Lee KH, Manos S, Lawley TJ. Expression and modulation of the vitronectin receptor on human dermal microvascular endothelial cells. J Invest Dermatol 1992; 99: 715-22.
13 Murphy JF, Bordet J-C, Wyler B, Rissoan M-C, Chomarat P, Defrance T, Miossec P, McGregor JL. The vitronectin receptor (α_vβ₃) is implicated, in cooperation with P-selectin and platelet-activating factor, in the adhesion of monocytes to activated endothelial cells. Biochem J 1994; 304: 537-42.
14 Enenstein J, Waleh NS, Kramer RH. Basic FGF and TGF-beta differentially modulate integrin expression of human microvascular endothelial cells. Exp Cell Res 1992; 203: 499-503.
15 Brown SL, Lundgren CH, Nordt T, Fujii S. Stimulation of migration of human aortic smooth muscle cells by vitronectin: implications for atherosclerosis. Cardiovasc Res 1994; 28: 1815-20.
16 Hoshiga M, Alpers CE, Smith LL, Giachelli CM, Schwartz SM. α_vβ₃ integrin expression in normal and atherosclerotic artery. Circ Res 1995; 77: 1129-35.
17 Krissansen GW, Lucas CM, Stomski FC, Elliott MJ, Berndt MC, Boyd AW, Horton MA, Cheresh DA, Vadas MA, Burns GF. Blood leukocytes bind platelet glycoprotein (IIb-IIIa) but do not express the vitronectin receptor. Int Immunol 1990; 2: 267-77.
18 Savill J, Dransfield I, Hogg N, Haslett C. Vitronectin receptor-mediated phagocytosis of cells undergoing apoptosis. Nature 1990; 343: 170-3.
19 Fadok VA, Savill JS, Haslett C, Bratton DL, Doherty DE, Campbell PA, Henson PM. Different populations of macrophages use either the vitronectin receptor or the phosphatidylserine receptor to recognize and remove apoptotic cells. J Immunol 1992; 149: 4029-35.
20 De Nichilo MO, Burns GF. Granulocyte-macrophage and macrophage colony-stimulating factors differentially regulate αv integrin expression on cultured human macrophages. Proc Natl Acad Sci USA 1993; 90: 2517-21.
21 Moulder K, Roberts K, Shevach EM, Coligan JE. The mouse vitronectin receptor is a T cell activation antigen. J Exp Med 1991; 173: 343.
22 Roberts K, Yokoyama WM, Kehn PJ, Shevach EM. The vitronectin receptor serves as an accessory molecule for the activation of a subset of gamma/δ T cells. J Exp Med 1991; 173: 231-40.
23 Roberts K, Shevach EM. Immunoregulatory role of gammaδ T cells. Ann N Y Acad Sci 1991; 636: 1-8.
24 Sturmhofel K, Brando C, Martinon F, Shevach EM, Coligan JE. Antigen-independent, integrin-mediated T cell activation. J Immunol 1995; 154: 2104-11.
25 Lawson MA, Maxfield FR. Ca²⁺- and calcineurin-dependent recycling of an integrin to the front of migrating neutrophils. Nature 1995; 377: 75-9.
26 Carreno M-P, 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.
27 Fitzgerald LA, Poncz M, Steiner B, Rall Jr. SC, Bennett JS, Phillips DR. Comparison of cDNA-derived protein sequences of the human fibronectin and vitronectin receptor alpha-subunits and platelet glycoprotein IIb. Biochemistry 1987; 26: 8158-65.
28 Fitzgerald LA, Charo IF, Phillips DR. Human and bovine endothelial cells synthesize membrane proteins similar to human platelet glycoproteins IIb and IIIa. J Biol Chem 1985; 260: 10893-6.
29 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 USA 1985; 83: 5766-70.
30 Suzuki S, Argraves WS, Pytela R, Arai H, Kruisius T, Pierschbacher MD, Ruoslahti E. cDNA and amino acid sequences of the cell adhesion protein receptor recognizing vitronectin reveal a transmembrane domain and homologies with other adhesion protein receptors. Proc Natl Acad Sci USA 1986; 83: 8614-8.
31 Filardo EJ, Cheresh DA. A β turn in the cytoplasmic tail of the integrin αv subunit influences conformation and ligand binding of α_vβ₃ . J Biol Chem 1994; 269: 4641-7.
32 Loftus JC, O’Toole TE, Plow EF, Glass A, Frelinger AL, Ginsberg MH. A β₃ integrin mutation abolishes ligand binding and alters divalent cation-dependent conformation. Science 1990; 249: 915-8.
33 Smith JW, Cheresh DA. Labeling of integrin alpha_vbeta₃ with ⁵⁸Co(III). J Biol Chem 1991; 266: 11429-32.
34 Fitzgerald LA, Steiner B, Rall Jr. SC, Lo SS, Phillips DR. Protein sequence of endothelial glycoprotein IIIa derived from a cDNA clone. J Biol Chem 1987; 262: 3936-9.
35 D’Souza SE, Haas TA, Piotrowicz RS, Byers-Ward V, McGrath DE, Soule HR, Cierniewski CS, Plow EF, Smith JW. Ligand and cation binding are dual functions of a discrete segment of the integrin beta-3 subunit: cation displacement from this site is implicated in ligand binding. Cell 1994; 79: 659-67.
36 Tozer EC, Liddington RC, Sutcliffe MJ, Smeeton AH, Loftus JC. Ligand binding to integrin α_IIbβ₃ is dependent on a MIDAS-like domain in the β₃ subunit. J Biol Chem 1996; 271: 21978-84.
37 Puzon-McLaughlin W, Takada Y. Critical residues for ligand binding in an I domain-like structure of the integrin β₁ subunit. J Biol Chem 1996; 271: 20438-43.
38 Lin CKE, Ratnikov BI, Tsai PM, Gonzalez ER, McDonald S, Pelletier AJ, Smith JW. Evidence that the integrin β₃ and β₅ subunits contain a metal ion-dependent adhesion site-like motif but lack an I domain. J Biol Chem 1997; 272: 14236-43.
39 Law DA, Nannizzi-Alaimo L, Phillips DR. Outside-in integrin signal transduction. α_IIbβ₃-(GPIIb-IIIa) tyrosine phosphorylation induced by platelet aggregation. J Biol Chem 1996; 271: 10811-5.
40 O’Toole TE, Ylanne J, Culley BM. Regulation of integrin affinity states through an NPXY motif in the β subunit cytoplasmic domain. J Biol Chem 1995; 270: 8553-8.
41 Haas TA, Plow EF. The cytoplasmic domain of α_IIbβ₃: a ternary complex of the integrin α and β subunits and a divalent cation. J Biol Chem 1996; 271: 6017-26.
42 Felding-Habermann B, Cheresh DA. Vitronectin and its receptors. Curr Opin Cell Biol 1993; 5: 864-8.
43 Charo IF, Nannizzi L, Smith JW, Cheresh DA. The vitronectin receptor α_vβ₃ binds fibronectin and acts in concert with α₅β₁ in promoting cellular attachment and spreading on fibronectin. J Cell Biol 1990; 111: 2795-800.
44 Kramer RH, Cheng Y-F, Clyman R. Human microvascular endothelial cells use β₁ and β₃ integrin receptor complexes to attach to laminin. J Cell Biol 1990; 111: 1233-43.
45 Lawler J, Weinstein R, Hynes RO. Cell attachment to thrombospondin: The role of arg-gly-asp, calcium and integrin receptors. J Cell Biol 1988; 107: 2351-61.
46 Denis C, Williams JA, Lu X, Meyer D, Baruch D. Solid-phase von Willebrand factor contains a conformationally active RGD motif that mediates endothelial cell adhesion through the α_vβ₃ receptor. Blood 1993; 82: 3622-30.
47 Sriramarao P, Mendler M, Bourdon MA. Endothelial cell attachment and spreading on human tenascin is mediated by α₂β₁ and α_vβ₃ integrins. J Cell Sci 1993; 105: 1001-12.
48 Miyauchi A, Alvarez J, Greenfield EM. et al. Recognition of osteopontin and related peptides by an α_vβ₃ integrin stimulates immediate cell signals in osteoclasts. J Biol Chem 1991; 266: 20369-74.
49 Horton MA, Taylor ML, Arnett TR, Helfrich MH. Arg-gly-asp (RGD) peptides and the anti-vitronectin receptor antibody 23C6 inhibit dentine resorption and cell spreading by osteoclasts. Exp Cell Res 1991; 195: 368-75.
50 Pfaff M, Aumailley M, Specks U, Knolle J, Zerwes H-G, Timpl R. Inte-grin and arg-gly-asp dependence of cell adhesion to the native and unfolded triple helix of collagen type VI. Exp Cell Res 1993; 206: 167-76.
51 Ruoslahti E, Pierschbacher MD. New perspectives in cell adhesion: RGD and integrins. Science 1987; 238: 491-7.
52 Ruoslahti E. RGD and other recognition sequences for integrins. Annu Rev Cell Biol 1996; 12: 697-715.
53 Cherny RC, Honan MA, Thiagarajan P. Site-directed mutagenesis of the arginine-glycine-aspartic acid in vitronectin abolishes cell adhesion. J Biol Chem 1993; 268: 9725-9.
54 Beacham DA, Wise RJ, Turci SM, Handin RI. Selective inactivation of the arg-gly-asp-ser (RGDS) binding site in von Willebrand factor by site-directed mutagenesis. J Biol Chem 1992; 267: 3409-15.
55 Montgomery AMP, Reisfeld RA, Cheresh DA. Integrin α_vβ₃ rescues melanoma cells from apoptosis in three-dimensional dermal collagen. Proc Natl Acad Sci USA 1994; 91: 8856-60.
56 Kanse SM, Kost C, Wilhelm OG, Andreasen PA, Preissner KT. The urokinase receptor is a major vitronectin-binding protein on endothelial cells. Exp Cell Res 1996; 224: 344-53.
57 Wei Y, Lukashev M, Simon DI, Bodary SC, Rosenberg S, Doyle MV, Chapman HA. Regulation of integrin function by the urokinase receptor. Science 1996; 273: 1551-5.
58 Yebra M, Parry GCN, Strömblad S, Mackman N, Rosenberg S, Mueller BM, Cheresh DA. Requirement of receptor-bound urokinase-type plasminogen activator for integrin α_vβ₅-directed cell migration. J Biol Chem 1996; 271: 29393-9.
59 Salonen E-M, Vaheri A, Pollanen J, Stephens R, Andreasen P, Mayer M, Dano K, Gailit J, Ruoslahti E. Interaction of plasminogen activator inhibitor (PAI-1) with vitronectin. J Biol Chem 1989; 264: 6339-43.
60 Stefansson S, Lawrence DA. The serpin PAI-1 inhibits cell migration by blocking integrin α_vβ₃ binding to vitronectin. Nature 1996; 383: 441-3.
61 Seiffert D, Loskutoff DJ. Type I plasminogen activator inhibitor induces multimerization of plasma vitronectin. A suggested mechanism for the generation of the tissue form of vitronectin in vivo. J Biol Chem 1996; 271: 29644-51.
62 Miles LA, Ginsberg MH, White JG, Plow EF. Plasminogen interacts with human platelets through two distinct mechanisms. J Clin Invest 1986; 77: 2001-9.
63 Brooks PC, Stromblad S, Sanders LC, von Schalscha TL, Aimes RT, Stetler-Stevenson WG, Quigley JP, Cheresh DA. Localization of matrix metalloproteinase MMP-2 to the surface of invasive cells by interaction with integrin α_vβ₃ . Cell 1996; 85: 683-93.
64 Brooks PC, Silletti S, von Schalscha TL, Friedlander M, Cheresh DA. Disruption of angiogenesis by PEX, a noncatalytic metalloproteinase fragment with integrin binding activity. Cell 1998; 92: 391-400.
65 Scarborough RM, Rose JW, Hsu MA, Phillips DR, Fried VA, Campbell AM, Nannizzi L, Charo IF. A GPIIb-IIIa-specific integrin antagonist from the venom of Sistrurus M, Barbouri. J Biol Chem 1991; 266: 9359-62.
66 Hu DD, Hoyer JR, Smith JW. Ca²⁺ suppresses cell adhesion to osteopontin by attenuating binding affinity for integrin α_vβ₃ . J Biol Chem 1995; 270: 9917-25.
67 Srivatsa SS, Fitzpatrick LA, Tsao PW, Reilly TM, Holmes Jr. DR, Schwartz RS, Mousa SA. Selective α_vβ₃ integrin blockade potently limits neointimal hyperplasia and lumen stenosis following deep coronary arterial stent injury: evidence for the functional importance of integrin α_vβ₃ and osteopontin expression during neointima formation. Cardiovasc Res 1998; 36: 408-28.
68 Lundgren CH, Sawa H, Fujii S. Inhibition of neointimal hyperplasia after balloon injury by local delivery of a cyclic arginine-glycine-aspartic acid peptide targeting vitronectin receptor [Abstract]. J Am Coll Cardiol 1995; 25: 83.
69 Pfaff M, Tangemann K, Müller B, Gurrath M, Müller G, Kessler H, Timpl R, Engel J. Selective recognition of cyclic RGD peptides of NMR defined conformation by α_IIbβ₃, α_vβ₃, and α₅β₁ integrins. J Biol Chem 1994; 269: 20233-8.
70 Lam SC-T, Plow EF, Smith MA, Andrieux A, Ryckwaert J-J, Marguerie G, Ginsberg MH. Evidence that arginine-glycine-aspartic acid and fibrinogen gamma chain peptides share a common binding site on platelets. J Biol Chem 1987; 262: 947-50.
71 Smith JW, Ruggeri ZM, Kunicki TJ, Cheresh DA. Interaction of integrins α_vβ₃ and glycoprotein IIb-IIIa with fibrinogen. J Biol Chem 1990; 265: 12267-71.
72 Felding-Habermann B, Ruggeri ZM, Cheresh DA. Distinct biological consequences of integrin α_vβ₃-mediated melanoma cell adhesion to fibrinogen and its plasmic fragments. J Biol Chem 1992; 267: 5070-7.
73 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; 58: 945-53.
74 Smith JW, Piotrowicz RS, Mathis D. A mechanism for divalent cation regulation of β₃-integrins. J Biol Chem 1994; 269: 960-7.
75 Gao AG, Lindberg FP, Dimitry JM, Brown EJ, Frazier WA. Thrombospondin modulates α_vβ₃ function through integrin-associated protein. J Cell Biol 1996; 135: 533-44.
76 Smith JW, Cheresh DA. The Arg-Gly-Asp binding domain of the vitronectin receptor. J Biol Chem 1988; 263: 18726-31.
77 D’Souza SE, Ginsberg MH, Lam SC-T, Plow EF. Chemical cross-linking of arginyl-glycyl-aspartic acid peptides to an adhesion receptor on platelets. J Biol Chem 1988; 263: 3943-51.
78 Loftus JC, Halloran CE, Ginsberg MH, Feigen LP, Zablocki JA, Smith JW. The amino-terminal one-third of α_IIb defines the ligand recognition specificity of integrin α_IIbβ₃ . J Biol Chem 1996; 271: 2033-9.
79 Savage B, Ruggeri ZM. Selective recognition of adhesive sites in surface-bound fibrinogen by glycoprotein IIb-IIIa on nonactivated platelets. J Biol Chem 1991; 266: 11227-33.
80 Gartner TK, Amrani DL, Derrick JM. Characterization of adhesion of nonexogenously stimulated and resting platelets in normal plasma to fibrinogen and its fragments. Blood Coagul Fibrinolysis 1994; 5: 747-54.
81 Schwartz MA, Schaller MD, Ginsberg MH. Integrins: Emerging paradigms of signal transduction. Annu Rev Cell Biol 1995; 11: 549-99.
82 Bennett JS, Vilaire G. Exposure of platelet fibrinogen receptors by ADP and epinephrine. J Clin Invest 1979; 64: 1393-401.
83 Marguerie GA, Plow EF, Edgington TS. Human platelets possess an inducible and saturable receptor specific for fibrinogen. J Biol Chem 1979; 254: 5357-63.
84 Faull RJ, Kovach NL, Harlan JM, Ginsberg MH. Affinity modulation of integrin α₅β₁: Regulation of the functional response by soluble fibronectin. J Cell Biol 1993; 121: 155-62.
85 Conforti G, Zanetti A, Pasquali-Ronchetti I, Quaglino Jr. D, Neyroz P, Dejana E. Modulation of vitronectin receptor binding by membrane lipid composition. J Biol Chem 1990; 265: 4011-9.
86 Buchanan MR, Bertomeu MC, Haas TA, Orr FW, Eltringham-Smith LL. Localization of 13-hydroxyoctadecadienoic acid and the vitronectin receptor in human endothelial cells and endothelial cell/platelet interactions in vitro. Blood 1993; 81: 3303-12.
87 Zanetti A, Conforti G, Hess S, Martìn-Padura I, Ghibaudi E, Preissner KT, Dejana E. Clustering of vitronectin and RGD peptides on microspheres leads to engagement of integrins on the luminal aspect of endothelial cell membrane. Blood 1994; 84: 1116-23.
88 Bennett JS, Chan C, Vilaire G, Mousa SA, DeGrado WF. Agonist-activated α_vβ₃ on platelets and lymphocytes binds to the matrix protein osteopontin. J Biol Chem 1997; 272: 8137-40.
89 Hato T, Pampori N, Shattil SJ. Complementary roles for receptor clustering and conformational change in the adhesive and signaling functions of integrin α_IIbβ₃ . J Cell Biol 1998; 141: 1685-95.
90 Shattil SJ, Ginsberg MH. Perspective Series: Cell adhesion in vascular biology. Integrin signaling in vascular biology. J Clin Invest 1997; 100: S91-S5.
91 Juliano RL, Haskill S. Signal transduction from the extracellular matrix. J Cell Biol 1993; 120: 577-85.
92 Lipfert L, Haimovich B, Schaller MD, Cobb BS, Parsons JT, Brugge JS. Integrin-dependent phosphorylation and activation of the protein tyrosine kinase pp125^fak in platelets. J Cell Biol 1992; 119: 905-12.
93 Shattil SJ, Haimovich B, Cunningham M, Lipfert L, Parsons JT, Ginsberg MH, Brugge JS. Tyrosine phosphorylation of pp125^FAK in platelets requires coordinated signaling through integrin and agonist receptors. J Biol Chem 1994; 269: 14738-45.
94 Ezumi Y, Takayama H, Okuma M. Differential regulation of protein-tyrosine phosphatases by integrin α_IIbβ₃ through cytoskeletal reorganization and tyro-sine phosphorylation in human platelets. J Biol Chem 1995; 270: 11927-34.
95 Furman MI, Grigoryev D, Bray PF, Dise KR, Goldschmidt-Clermont PJ. Platelet tyrosine kinases and fibrinogen receptor activation. Circ Res 1994; 75: 172-80.
96 Jackson SP, Schoenwaelder SM, Yuan YP, Salem HH, Cooray P. Non-receptor protein tyrosine kinases and phosphatases in human platelets. Thromb Haemost 1996; 76: 640-50.
97 Gao J, Zoller KE, Ginsberg MH, Brugge JS, Shattil SJ. Regulation of the pp72^syk protein tyrosine kinase by platelet integrin α_IIbβ₃ . EMBO J 1997; 16: 6414-25.
98 Blystone SD, Williams MP, Slater SE, Brown EJ. Requirement of integrin β₃ tyrosine 747 for β₃ tyrosine phosphorylation and regulation of α_vβ₃ avidity. J Biol Chem 1997; 272: 28757-61.
99 Schwartz MA. Spreading of human endothelial cells on fibronectin or vitronectin triggers elevation of intracellular free calcium. J Cell Biol 1993; 120: 1003-10.
100 Shanker S, Davison I, Mason WT, Horton MA. Integrin receptor mediated mobilization of intranuclear calcium in rat osteoclasts. J Cell Sci 1993; 105: 61-8.
101 Schwartz MA, Brown EJ, Fazeli B. A 50-kDa integrin-associated protein is required for integrin-regulated calcium entry in endothelial cells. J Biol Chem 1993; 268: 19931-4.
102 Cooper D, Lindberg FP, Gamble JR, Brown EJ, Vadas MA. The transendothelial migration of neutrophils involves integrin associated protein (CD47). Proc Natl Acad Sci USA 1995; 92: 3978-82.
103 Schwartz MA, Denninghoff K. α_v Integrins mediate the rise in intracellular calcium in endothelial cells on fibronectin even though they play a minor role in adhesion. J Biol Chem 1994; 269: 11133-7.
104 Anikumar N, Bhattacharya AK, Manogaran PS, Pande G. Modulation of α_vβ₁ and α_vβ₃ integrins on the cell surface during mitosis. J Cell Biochem 1996; 61: 338-49.
105 Brooks PC. Cell adhesion molecules in angiogenesis. Cancer Metastasis Rev 1996; 15: 187-94.
106 Stromblad S, Becker JC, Yebra M, Brooks PC, Cheresh DA. Suppression of p53 activity and p21^WAFI/CIPI expression by vascular cell integrin α_vβ₃ during angiogenesis. J Clin Invest 1996; 98: 426-33.
107 Brooks PC, Clark RA, Cheresh DA. Requirement of vascular integrin α_vβ₃ for angiogenesis. Science 1994; 264: 569-71.
108 Brooks PC, Montgomery AM, Rosenfeld M, Reisfeld RA, Hu T, Klier G, Cheresh DA. Integrin α_vβ₃ antagonists promote tumor regression by inducing apoptosis of angiogenic blood vessels. Cell 1994; 79: 1157-64.
109 Bartfeld NS, Pasquale EB, Geltosky JE, Languino LR. The α_vβ₃ integrin associates with a 190-kDa protein that is phosphorylated on tyrosine in response to platelet-derived growth factor. J Biol Chem 1993; 268: 17270-6.
110 Schneller M, Vuori K, Ruoslahti E. α_vβ₃ integrin associates with activated insulin and PDGFβ receptors and potentiates the biological activity of PDGF. EMBO J 1997; 16: 5600-7.
111 Bhattacharya S, Fu C, Bhattacharya J, Greenberg S. Soluble ligands of the α_vβ₃ integrin mediate enhanced tyrosine phosphorylation of multiple proteins in adherent bovine pulmonary artery endothelial cells. J Biol Chem 1996; 270: 16781-7.
112 Blystone SD, Lindberg FP, Williams MP, McHugh KP, Brown EJ. Inducible tyrosine phosphorylation of the β₃ integrin requires the α_v integrin cytoplasmic tail. J Biol Chem 1996; 271: 31458-62.
113 Wu H, Parsons JT. Cortactin, an 80/85-kilodalton pp60^src substrate, is a filamentous actin-binding protein enriched in the cell cortex. J Cell Biol 1993; 120: 1417-26.
114 Wary KK, Mainiero F, Isakoff SJ, Marcantonio EE, Giancotti FG. The adaptor protein Shc couples a class of integrins to the control of cell cycle progression. Cell 1996; 87: 733-43.
115 Ginsberg MH, Loftus J, Ryckwaert J-J, Pierschbacher M, Pytela R, Ruoslahti E, Plow EF. Immunochemical and amino-terminal sequence comparison of two cytoadhesins indicates they contain similar or identical beta subunits and distinct alpha subunits. J Biol Chem 1987; 262: 5437-40.
116 Liaw L, Skinner MP, Raines EW, Ross R, Cheresh DA, Schwartz SM, Giachelli CM. The adhesive and migratory effects of osteopontin are mediated via distinct cell surface integrins: role of α_vβ₃ in smooth muscle cell migration to osteopontin in vitro. J Clin Invest 1995; 95: 713-24.
117 Matsuno H, Stassen JM, Moons L, Vermylen J, Hoylaerts MF. Neointima formation in injured hamster carotid artery is effectively prevented by the combination G4120 and quinapril. Thromb Haemost 1996; 76: 263-9.
118 Liaw L, Almeida M, Hart CE, Schwartz SM, Giachelli CM. Osteopontin promotes vascular cell adhesion and spreading and is chemotactic for smooth muscle cells in vitro. Circ Res 1994; 74: 214-24.
119 Choi ET, Engel L, Callow AD, Sun S, Trachtenberg J, Santoro S, Ryan US. Inhibition of neointimal hyperplasia by blocking α_vβ₃ integrin with a small peptide antagonist GpenGRGDSPCA. J Vasc Surg 1994; 19: 125-34.
120 Leavesley DI, Schwartz MA, Rosenfeld M, Cheresh DA. Integrin β₁- and β₃-mediated endothelial cell migration is triggered through distinct signaling mechanisms. J Cell Biol 1993; 121: 163-70.
121 Jones JI, Prevette T, Gockerman A, Clemmons DR. Ligand occupancy of the α_vβ₃ integrin is necessary for smooth muscle cells to migrate in response to insulin-like growth factor I. Proc Natl Acad Sci USA 1996; 93: 2482-7.
122 Matsuno H, Stassen JM, Vermylen J, Deckmyn H. Inhibition of integrin function by a cyclic RGD-containing peptide prevents neointima formation. Circulation 1994; 90: 2203-6.
123 LeBreton H, Rabbani R, Plow E, Mousa S, Lincoff AM, Forudi F, Topol EJ. The role of integrin α_IIbβ₃ and α_vβ₃ in a guinea pig model of restenosis [Abstract]. Circulation 1996; 94: I-517.
124 van der Zee R, Passeri J, Barry JJ, Cheresh DA, Isner JM. A neutralizing antibody to the α_vβ₃ integrin reduces neointimal thickening in a balloon-injured rabbit iliac artery [Abstract]. Circulation 1996; 94: I-257.
125 Topol EJ, Califf RM, Weisman HF, Ellis SG, Tcheng JE, Worley S, Ivanhoe R, George BS, Fintel D, Weston M, Sigmon K, Anderson KM, Lee KL, Willerson JT. Randomised trial of coronary intervention with antibody against platelet IIb/IIIa integrin for reduction of clinical restenosis: Results at six months. Lancet 1994; 343: 881-6.
126 Tcheng JE, Harrington RA, Kottke-Marchant K, Kleiman NS, Ellis SG, Kereiakes DJ, Mick MJ, Navetta FI, Smith JE, Worley SJ, Miller JA, Joseph DM, Sigmon KN, Kitt MM, du Mee CP, Califf RM, Topol EJ. Multicenter, randomized, double-blind, placebo-controlled trial of the platelet integrin glycoprotein IIb/IIIa blocker Integrelin in elective coronary intervention. IMPACT Investigators. Circulation 1995; 91: 2151-7.
127 The EPILOG Investigators.. Platelet glycoprotein IIb/IIIa receptor blockade and low-dose heparin during percutaneous coronary revascularization. N Engl J Med 1997; 336: 1689-96.
128 Friedlander M, Brooks PC, Shaffer RW, Kincaid CM, Varner JA, Cheresh DA. Definition of two angiogenic pathways by distinct α_v integrins. Science 1995; 270: 1500-2.
129 Hammes HP, Brownlee M, Jonczyk A, Sutter A, Preissner KT. Subcutaneous injection of a cyclic peptide antagonist of vitronectin receptor-type integrins inhibits retinal neovascularization. Nature Med 1996; 2: 529-33.
130 Hodivala-Dilke KM, McHugh K, Tsakiris DA, Rayburn H, Ross FP, Coller BS, Teitelbaum S, Hynes RO. β₃ integrin knockout mice display a Glanzmann thrombasthenia phenotype [Abstract]. Blood 1997; 90: 2550a.
131 Katagiri Y, Hiroyama T, Akamatsu N, Suzuki H, Yamazaki H, Tanoue K. Involvement of α_vβ₃ integrin in mediating fibrin gel retraction. J Biol Chem 1995; 270: 1785-90.
132 Chen Y, O’Toole TE, Leong L, Liu B, Diaz-Gonzalez F, Ginsberg MH. β₃ integrin-mediated fibrin clot retraction by nucleated cells: differing behavior of α_IIbβ₃ and α_vβ₃ . Blood 1995; 86: 2606-15.
133 Mogford JE, Davis GE, Platts SH, Meininger GA. Vascular smooth muscle α_vβ₃ integrin mediates arteriolar vasodilation in response to RGD peptides. Circ Res 1996; 79: 821-6.
134 Winocour PD, Richardson M, Kinlough-Rathbone RL. Continued platelet interaction with de-endothelialized aortae associated with slower re-endothelialization and more extensive intimal hyperplasia in spontaneously diabetic BB Wistar rats. Int J Exp Pathol 1993; 74: 603-13.
135 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. Identification and characterization with monoclonal antibodies. J Exp Med 1989; 169: 2173-90.
136 Lam SC, Plow EF, D’Souza SE, Cheresh DA, Frelinger AL, III Ginsberg MH. Isolation and characterization of a platelet membrane protein related to the vitronectin receptor. J Biol Chem 1989; 264: 3742-9.
137 Coller BS, Cheresh DA, Asch E, Seligsohn U. Platelet vitronectin receptor expression differentiates Iraqi-Jewish from Arab patients with Glanzmann thrombasthenia in Israel. Blood 1991; 77: 75-83.
138 Clark RAF, Tonnesen MG, Gailit J, Cheresh DA. Transient functional expression of α_vβ₃ on vascular cells during wound repair. Am J Pathol 1996; 148: 1407-21.