Gene Symbol: ITGA4
Description: integrin subunit alpha 4
Alias: CD49D, IA4, integrin alpha-4, 269C wild type, CD49 antigen-like family member D, VLA-4 subunit alpha, alpha 4 subunit of VLA-4 receptor, antigen CD49D, alpha-4 subunit of VLA-4 receptor, integrin alpha-IV, very late activation protein 4 receptor, alpha 4 subunit
Species: human
Products:     ITGA4

Top Publications

  1. Kleinewietfeld M, Starke M, Di Mitri D, Borsellino G, Battistini L, Rotzschke O, et al. CD49d provides access to "untouched" human Foxp3+ Treg free of contaminating effector cells. Blood. 2009;113:827-36 pubmed publisher
    ..Here we show that clean populations of human Foxp3(+) Treg cells can be obtained with antibodies directed against CD49d. The marker is present on proinflammatory peripheral blood mononuclear cells but is absent on immune-suppressive ..
  2. Till K, Spiller D, Harris R, Chen H, Zuzel M, Cawley J. CLL, but not normal, B cells are dependent on autocrine VEGF and alpha4beta1 integrin for chemokine-induced motility on and through endothelium. Blood. 2005;105:4813-9 pubmed
    ..Given the importance of cell motility for tissue invasion, the present results provide a rationale for a trial of VEGF and alpha(4) blockade in patients with CLL who have tissue disease. ..
  3. Oostendorp R, Dormer P. VLA-4-mediated interactions between normal human hematopoietic progenitors and stromal cells. Leuk Lymphoma. 1997;24:423-35 pubmed
    ..Moreover, these insights may explain how defects in adhesive behavior of leukemic HPC through VLA-4 contribute to their dysregulated growth and provide a rationale for therapeutically correcting those defects. ..
  4. Liu S, Thomas S, Woodside D, Rose D, Kiosses W, Pfaff M, et al. Binding of paxillin to alpha4 integrins modifies integrin-dependent biological responses. Nature. 1999;402:676-81 pubmed
    ..Thus, the tight association of paxillin with the alpha4 tail leads to distinct biochemical and biological responses to integrin-mediated cell adhesion. ..
  5. Till K, Lin K, Zuzel M, Cawley J. The chemokine receptor CCR7 and alpha4 integrin are important for migration of chronic lymphocytic leukemia cells into lymph nodes. Blood. 2002;99:2977-84 pubmed
    ..The present studies are the first to shed light on the factors determining CLL cell entry into nodes and define the phenotype of circulating malignant cells likely to determine the pattern of lymph node enlargement in the disease. ..
  6. Jelicic K, Cimbro R, Nawaz F, Huang D, Zheng X, Yang J, et al. The HIV-1 envelope protein gp120 impairs B cell proliferation by inducing TGF-β1 production and FcRL4 expression. Nat Immunol. 2013;14:1256-65 pubmed publisher
    ..Our studies identify a mechanism whereby the virus may subvert the early HIV-1-specific humoral immune response. ..
  7. Chigaev A, Zwartz G, Graves S, Dwyer D, Tsuji H, Foutz T, et al. Alpha4beta1 integrin affinity changes govern cell adhesion. J Biol Chem. 2003;278:38174-82 pubmed
    ..Taken together, these data are consistent with the idea that affinity regulation is a major factor that governs the avidity of cell adhesion mediated by the alpha4 integrin. ..
  8. Arthos J, Cicala C, Martinelli E, Macleod K, Van Ryk D, Wei D, et al. HIV-1 envelope protein binds to and signals through integrin alpha4beta7, the gut mucosal homing receptor for peripheral T cells. Nat Immunol. 2008;9:301-9 pubmed publisher
    ..On CD4+ T cells, engagement of alpha4beta7 by gp120 resulted in rapid activation of LFA-1, the central integrin involved in the establishment of virological synapses, which facilitate efficient cell-to-cell spreading of HIV-1. ..
  9. Brittain J, Han J, Ataga K, Orringer E, Parise L. Mechanism of CD47-induced alpha4beta1 integrin activation and adhesion in sickle reticulocytes. J Biol Chem. 2004;279:42393-402 pubmed
    ..These studies therefore identify the alpha4beta1 integrin on SS RBCs as a CD47-activated receptor for TSP, VCAM-1, and plasma fibronectin, revealing novel binding characteristics of this integrin. ..

More Information


  1. Rose D, Han J, Ginsberg M. Alpha4 integrins and the immune response. Immunol Rev. 2002;186:118-24 pubmed
    ..Furthermore, this protein-protein interaction may provide novel targets for the modulation of the immune response. ..
  2. Nuckel H, Switala M, Collins C, Sellmann L, Grosse Wilde H, Duhrsen U, et al. High CD49d protein and mRNA expression predicts poor outcome in chronic lymphocytic leukemia. Clin Immunol. 2009;131:472-80 pubmed publisher
    b>CD49d plays a critical role in leucocyte trafficking, activation and survival, and facilitates interactions between leucocytes and stromal cells. Recent data give evidence for the prognostic relevance of CD49d protein expression in B-CLL...
  3. Chigaev A, Zwartz G, Buranda T, Edwards B, Prossnitz E, Sklar L. Conformational regulation of alpha 4 beta 1-integrin affinity by reducing agents. "Inside-out" signaling is independent of and additive to reduction-regulated integrin activation. J Biol Chem. 2004;279:32435-43 pubmed
    The alpha(4)beta(1)-integrin (very late antigen-4 (VLA-4), CD49d/CD29) is an adhesion receptor involved in the interaction of lymphocytes, dendritic cells, and stem cells with the extracellular matrix and endothelial cells...
  4. Gattei V, Bulian P, Del Principe M, Zucchetto A, Maurillo L, Buccisano F, et al. Relevance of CD49d protein expression as overall survival and progressive disease prognosticator in chronic lymphocytic leukemia. Blood. 2008;111:865-73 pubmed
    b>CD49d/alpha4-integrin is variably expressed in chronic lymphocytic leukemia (CLL)...
  5. Garmy Susini B, Avraamides C, Schmid M, Foubert P, Ellies L, Barnes L, et al. Integrin alpha4beta1 signaling is required for lymphangiogenesis and tumor metastasis. Cancer Res. 2010;70:3042-51 pubmed publisher
  6. Brachtl G, Sahakyan K, Denk U, Girbl T, Alinger B, Hofbauer S, et al. Differential bone marrow homing capacity of VLA-4 and CD38 high expressing chronic lymphocytic leukemia cells. PLoS ONE. 2011;6:e23758 pubmed publisher
    ..Our data argue for a prominent role of VLA-4 but not CD38 expression in the homing of CLL cells to BM niches and in human BM infiltration, but only a limited role in their protection by stromal cells. ..
  7. Redondo Muñoz J, Ugarte Berzal E, Garcia Marco J, Del Cerro M, Van Den Steen P, Opdenakker G, et al. Alpha4beta1 integrin and 190-kDa CD44v constitute a cell surface docking complex for gelatinase B/MMP-9 in chronic leukemic but not in normal B cells. Blood. 2008;112:169-78 pubmed publisher
    ..Thus, we have identified alpha4beta1 and CD44v as a novel proMMP-9 cell surface docking complex and show that cell-associated MMP-9 may regulate B-CLL cell migration and arrest. ..
  8. Hyduk S, Cybulsky M. Alpha 4 integrin signaling activates phosphatidylinositol 3-kinase and stimulates T cell adhesion to intercellular adhesion molecule-1 to a similar extent as CD3, but induces a distinct rearrangement of the actin cytoskeleton. J Immunol. 2002;168:696-704 pubmed
    ..Qualitatively similar morphological and adhesive changes to those observed with Jurkat cells were observed following alpha(4) integrin or CD3 stimulation of human peripheral blood T cells. ..
  9. Serru V, Le Naour F, Billard M, Azorsa D, Lanza F, Boucheix C, et al. Selective tetraspan-integrin complexes (CD81/alpha4beta1, CD151/alpha3beta1, CD151/alpha6beta1) under conditions disrupting tetraspan interactions. Biochem J. 1999;340 ( Pt 1):103-11 pubmed
    ..Because all tetraspan-tetraspan associations are disrupted by digitonin, it is likely that the other tetraspans interact indirectly with integrins, through interactions with CD81 or CD151. ..
  10. Chen J, Takagi J, Xie C, Xiao T, Luo B, Springer T. The relative influence of metal ion binding sites in the I-like domain and the interface with the hybrid domain on rolling and firm adhesion by integrin alpha4beta7. J Biol Chem. 2004;279:55556-61 pubmed
    ..Overall, the results demonstrate the importance of headpiece allostery in the conversion of rolling to firm adhesion. ..
  11. Alon R, Feigelson S, Manevich E, Rose D, Schmitz J, Overby D, et al. Alpha4beta1-dependent adhesion strengthening under mechanical strain is regulated by paxillin association with the alpha4-cytoplasmic domain. J Cell Biol. 2005;171:1073-84 pubmed
  12. Han J, Liu S, Rose D, Schlaepfer D, McDonald H, Ginsberg M. Phosphorylation of the integrin alpha 4 cytoplasmic domain regulates paxillin binding. J Biol Chem. 2001;276:40903-9 pubmed
    ..Consequently, alpha4 phosphorylation is a biochemical mechanism to modulate paxillin binding to alpha4 integrins with consequent regulation of alpha4 integrin-dependent cellular functions. ..
  13. de Bruyn K, Rangarajan S, Reedquist K, Figdor C, Bos J. The small GTPase Rap1 is required for Mn(2+)- and antibody-induced LFA-1- and VLA-4-mediated cell adhesion. J Biol Chem. 2002;277:29468-76 pubmed
    ..We suggest that Rap1 determines the functional availability of integrins for productive binding to integrin ligands. ..
  14. Mannion B, Berditchevski F, Kraeft S, Chen L, Hemler M. Transmembrane-4 superfamily proteins CD81 (TAPA-1), CD82, CD63, and CD53 specifically associated with integrin alpha 4 beta 1 (CD49d/CD29). J Immunol. 1996;157:2039-47 pubmed
    ..In reciprocal experiments, the integrin alpha 4 beta 1 (VLA4, CD49d/CD29) could be reprecipitated from CD81 immunoprecipitates...
  15. Cicala C, Martinelli E, McNally J, Goode D, Gopaul R, Hiatt J, et al. The integrin alpha4beta7 forms a complex with cell-surface CD4 and defines a T-cell subset that is highly susceptible to infection by HIV-1. Proc Natl Acad Sci U S A. 2009;106:20877-82 pubmed publisher
    ..The specific affinity of gp120 for alpha(4)beta(7) provides a mechanism for HIV-1 to target activated cells that are critical for efficient virus propagation and dissemination following sexual transmission. ..
  16. Rossi D, Zucchetto A, Rossi F, Capello D, Cerri M, Deambrogi C, et al. CD49d expression is an independent risk factor of progressive disease in early stage chronic lymphocytic leukemia. Haematologica. 2008;93:1575-9 pubmed publisher
    ..We analyzed CD49d expression in 140 consecutive Binet A chronic lymphocytic leukemia. At diagnosis, CD49d >or=30% (54/140, 38...
  17. Reitano K, Kottilil S, Gille C, Zhang X, Yan M, O Shea M, et al. Defective plasmacytoid dendritic cell-NK cell cross-talk in HIV infection. AIDS Res Hum Retroviruses. 2009;25:1029-37 pubmed publisher
    ..These findings suggest a novel mechanism by which HIV is capable of suppressing an innate immune function in infected individuals. ..
  18. Nguyen K, Sylvain N, Bunnell S. T cell costimulation via the integrin VLA-4 inhibits the actin-dependent centralization of signaling microclusters containing the adaptor SLP-76. Immunity. 2008;28:810-21 pubmed publisher
    ..These data suggest a widely applicable model of costimulation, in which integrins promote sustained signaling by attenuating cytoskeletal movements that drive the centralization and inactivation of SLP-76 microclusters. ..
  19. Moog Lutz C, Cavé Riant F, Guibal F, Breau M, Di Gioia Y, Couraud P, et al. JAML, a novel protein with characteristics of a junctional adhesion molecule, is induced during differentiation of myeloid leukemia cells. Blood. 2003;102:3371-8 pubmed
    ..Altogether, our results point to JAML as a novel member of the JAM family expressed on leukocytes with a possible role in leukocyte transmigration. ..
  20. Rose D, Liu S, Woodside D, Han J, Schlaepfer D, Ginsberg M. Paxillin binding to the alpha 4 integrin subunit stimulates LFA-1 (integrin alpha L beta 2)-dependent T cell migration by augmenting the activation of focal adhesion kinase/proline-rich tyrosine kinase-2. J Immunol. 2003;170:5912-8 pubmed
  21. Redondo Muñoz J, Ugarte Berzal E, Terol M, Van Den Steen P, Hernández Del Cerro M, Roderfeld M, et al. Matrix metalloproteinase-9 promotes chronic lymphocytic leukemia b cell survival through its hemopexin domain. Cancer Cell. 2010;17:160-72 pubmed publisher
    ..Our results establish that MMP/receptor binding induces intracellular survival signals and highlight the role of (pro)MMP-9 in B-CLL pathogenesis. ..
  22. Hsia D, Lim S, Bernard Trifilo J, Mitra S, Tanaka S, den Hertog J, et al. Integrin alpha4beta1 promotes focal adhesion kinase-independent cell motility via alpha4 cytoplasmic domain-specific activation of c-Src. Mol Cell Biol. 2005;25:9700-12 pubmed
  23. Nawaz F, Cicala C, Van Ryk D, Block K, Jelicic K, McNally J, et al. The genotype of early-transmitting HIV gp120s promotes ? (4) ?(7)-reactivity, revealing ? (4) ?(7) +/CD4+ T cells as key targets in mucosal transmission. PLoS Pathog. 2011;7:e1001301 pubmed publisher
    ..Understanding the structural features that characterize early-transmitting gp120s may aid in the design of an effective gp120-based subunit vaccine. ..
  24. Rosemblatt M, Vuillet Gaugler M, Leroy C, Coulombel L. Coexpression of two fibronectin receptors, VLA-4 and VLA-5, by immature human erythroblastic precursor cells. J Clin Invest. 1991;87:6-11 pubmed
    ..Furthermore, monoclonal antibodies recognizing the VLA alpha 4 chain blocked the adhesion of immature erythroblasts to Fn-coated surfaces, thus demonstrating that, as VLA-5, VLA-4 is also a functional Fn receptor on these cells. ..
  25. Mittelbrunn M, Molina A, Escribese M, Yanez Mo M, Escudero E, Ursa A, et al. VLA-4 integrin concentrates at the peripheral supramolecular activation complex of the immune synapse and drives T helper 1 responses. Proc Natl Acad Sci U S A. 2004;101:11058-63 pubmed
    The integrin alpha 4 beta 1 (VLA-4) not only mediates the adhesion and transendothelial migration of leukocytes, but also provides costimulatory signals that contribute to the activation of T lymphocytes...
  26. Binsky I, Lantner F, Grabovsky V, Harpaz N, Shvidel L, Berrebi A, et al. TAp63 regulates VLA-4 expression and chronic lymphocytic leukemia cell migration to the bone marrow in a CD74-dependent manner. J Immunol. 2010;184:4761-9 pubmed publisher
    ..These results could form the basis of novel therapeutic strategies aimed at blocking homing of CLL cells in their return to the BM and attenuating their survival. ..
  27. Majid A, Lin T, Best G, Fishlock K, Hewamana S, Pratt G, et al. CD49d is an independent prognostic marker that is associated with CXCR4 expression in CLL. Leuk Res. 2011;35:750-6 pubmed publisher
    ..One such marker that fulfils both of these criteria is the integrin CD49d. This molecule been implicated in the capacity of CLL cells to migrate into lymphoid tissues and there is a CD49d ..
  28. Evans C, Orf K, Horváth E, Levin M, de la Fuente J, Chakravorty S, et al. Impairment of neutrophil oxidative burst in children with sickle cell disease is associated with heme oxygenase-1. Haematologica. 2015;100:1508-16 pubmed publisher
    ..cell disease, but not in healthy children, with a surface marker profile consistent with neutrophil progenitors (CD49d(Hi) CD24(Lo) CD15(Int) CD16(Int) CD11b(+/-))...
  29. Reindel R, Baker S, Kim K, Rowley C, Shulman S, Orenstein J, et al. Integrins ?4 and ?M, collagen1A1, and matrix metalloproteinase 7 are upregulated in acute Kawasaki disease vasculopathy. Pediatr Res. 2013;73:332-6 pubmed publisher
    ..Integrins ?4 and ?M (ITGA4, ITGAM), collagen type I, ?1 (COL1A1), and matrix metalloproteinase 7 (MMP7) were significantly upregulated in KD ..
  30. Ko S, Park C, Park S, Cho Y, Jang S, Seo E, et al. High CXCR4 and low VLA-4 expression predicts poor survival in adults with acute lymphoblastic leukemia. Leuk Res. 2014;38:65-70 pubmed publisher
    ..02). Expression levels of CXCR4 and VLA-4 did not predict patient prognosis in children. Analysis of CXCR4 and VLA-4 expression at diagnosis in adults with ALL can provide useful information on patient prognosis. ..
  31. Boroujerdnia M, Dezfuly F, Mosthophy N. An immunohistochemical study of beta1 integrin molecules (VLA-4, VLA-5, VLA-6) in all endometrial compartments of fertile and infertile women in Ahwaz-Iran. Pak J Biol Sci. 2009;12:360-6 pubmed
  32. Brittain J, Parise L. The alpha4beta1 integrin in sickle cell disease. Transfus Clin Biol. 2008;15:19-22 pubmed publisher
    ..We also illustrate novel therapies in SCD that may target the integrin and alleviate vaso-occlusion. ..
  33. Liu C, Leclair P, Yap S, Lim C. The membrane-proximal KXGFFKR motif of ?-integrin mediates chemoresistance. Mol Cell Biol. 2013;33:4334-45 pubmed publisher
    ..The ?-integrin KXGFFKR motif is involved in adhesion-mediated control of chemoresistance in T cells. ..
  34. Domínguez Jiménez C, Sánchez Aparicio P, Albar J, Garcia Pardo A. The alpha 4 beta 1 fibronectin ligands CS-1, Hep II, and RGD induce different intracellular events in B lymphoid cells. Comparison with the effects of the endothelial ligand VCAM-1. Cell Adhes Commun. 1996;4:251-67 pubmed
    The lymphocyte integrin alpha 4 beta 1 is the receptor for the Hep II domain and CS-1 site in fibronectin (Fn) as well as for VCAM-1...
  35. Nibali L, Novoa L, Donos N, Henderson B, Blanco J, Tomas I. Leukocyte receptor expression in chronic periodontitis. Clin Oral Investig. 2016;20:2559-2564 pubmed publisher
    ..for the determination of the expression of 16 leukocyte receptors (CD4, CD8, CD11b, CD14, CD16, CD19, CD25, CD28, CD49d, CD49e, CD62, CD71, CD80, CCR7, Ly6G and HLA-DR)...
  36. Tassaneetrithep B, Tivon D, Swetnam J, Karasavvas N, Michael N, Kim J, et al. Cryptic determinant of α4β7 binding in the V2 loop of HIV-1 gp120. PLoS ONE. 2014;9:e108446 pubmed publisher
    ..Accordingly, the anti-V2 antibodies that apparently reduced the risk of infection in the RV144 trial may have functioned by blocking α4β7-mediated HIV-host cell interactions via this cryptic determinant. ..
  37. Boehmler A, Drost A, Jaggy L, Seitz G, Wiesner T, Denzlinger C, et al. The CysLT1 ligand leukotriene D4 supports alpha4beta1- and alpha5beta1-mediated adhesion and proliferation of CD34+ hematopoietic progenitor cells. J Immunol. 2009;182:6789-98 pubmed publisher
    ..Our results suggest that cysteinyl leukotriene may contribute to HPC retention and proliferation only when cysteinyl leukotriene levels are increased either systemically during inflammation or locally during marrow aplasia. ..
  38. Estin M, Thompson S, Traxinger B, Fisher M, Friedman R, Jacobelli J. Ena/VASP proteins regulate activated T-cell trafficking by promoting diapedesis during transendothelial migration. Proc Natl Acad Sci U S A. 2017;114:E2901-E2910 pubmed publisher
    ..Deletion of EVL and VASP resulted in the impairment in ?4 integrin (CD49d) expression and function...
  39. Zhang Y, Hou Y, Wang X, Ping J, Ma Z, Suo C, et al. The effects of kisspeptin-10 on serum metabolism and myocardium in rats. PLoS ONE. 2017;12:e0179164 pubmed publisher
    ..These genes were enriched in several signaling pathways related to heart diseases. The RT-PCR result for ITGB8, ITGA4, ITGB7, MYL7, HIF1-? and BNP corresponded with the gene chip assay...
  40. Feito M, Bragardo M, Buonfiglio D, Bonissoni S, Bottarel F, Malavasi F, et al. gp 120s derived from four syncytium-inducing HIV-1 strains induce different patterns of CD4 association with lymphocyte surface molecules. Int Immunol. 1997;9:1141-7 pubmed
    ..All gp120s induced significant CD4 association with CD49d, but gp120SF2 displayed a significantly weaker effect than gp120IIIB...
  41. Fujita M, Takada Y, Takada Y. Integrins ?v?3 and ?4?1 act as coreceptors for fractalkine, and the integrin-binding defective mutant of fractalkine is an antagonist of CX3CR1. J Immunol. 2012;189:5809-19 pubmed publisher
    ..These findings suggest that K36E/R37E acts as a dominant-negative CX3CR1 antagonist and that FKN-CD/integrin interaction is a novel therapeutic target in inflammatory diseases. ..
  42. Glatigny S, Wagner C, Bettelli E. Cutting Edge: Integrin ?4 Is Required for Regulatory B Cell Control of Experimental Autoimmune Encephalomyelitis. J Immunol. 2016;196:3542-6 pubmed publisher
    The neutralization of integrin ?4 (Itga4) is currently used as treatment in multiple sclerosis...
  43. Girard A, Vergnon Miszczycha D, Depincé Berger A, Roblin X, Lutch F, Lambert C, et al. Brief Report: A High Rate of β7+ Gut-Homing Lymphocytes in HIV-Infected Immunological Nonresponders is Associated With Poor CD4 T-Cell Recovery During Suppressive HAART. J Acquir Immune Defic Syndr. 2016;72:259-65 pubmed publisher
    ..These results emphasize the great interest to consider α4β7-targeted therapy in INR patients to block homing of lymphocytes and/or to directly impair gp120-α4β7 interactions. ..
  44. Kolesnikova T, Stipp C, Rao R, Lane W, Luscinskas F, Hemler M. EWI-2 modulates lymphocyte integrin alpha4beta1 functions. Blood. 2004;103:3013-9 pubmed
    ..We suggest that EWI-2-dependent reorganization of alpha4beta1-CD81 complexes on the cell surface is responsible for EWI-2 effects on integrin-dependent morphology and motility functions. ..
  45. McLinden R, LaBranche C, Chenine A, Polonis V, Eller M, Wieczorek L, et al. Detection of HIV-1 neutralizing antibodies in a human CD4?/CXCR4?/CCR5? T-lymphoblastoid cell assay system. PLoS ONE. 2013;8:e77756 pubmed publisher
    ..The A3R5 cell line provides a novel approach to guide the development and qualification of promising new HIV-1 vaccine immunogens. ..
  46. Jiang A, Jiang J, Guo M, Jin Y, Li Y, Wang J. Human Blood-Circulating Basophils Capture HIV-1 and Mediate Viral trans-Infection of CD4+ T Cells. J Virol. 2015;89:8050-62 pubmed publisher
    ..We suggest that strategies designed to prevent basophil-mediated viral capture and transfer may be a new direction for the development of anti-HIV therapy. ..
  47. Khurana S, Buckley S, Schouteden S, Ekker S, Petryk A, Delforge M, et al. A novel role of BMP4 in adult hematopoietic stem and progenitor cell homing via Smad independent regulation of integrin-?4 expression. Blood. 2013;121:781-90 pubmed publisher
    ..KLS) and CD150CD48-KLS cells for up to 5 days in vitro prevented the culture-induced loss of Integrin-?4 (ITGA4) expression as well as homing...
  48. Sullivan G, Lee D, Ross W, DiVietro J, Lappas C, Lawrence M, et al. Activation of A2A adenosine receptors inhibits expression of alpha 4/beta 1 integrin (very late antigen-4) on stimulated human neutrophils. J Leukoc Biol. 2004;75:127-34 pubmed
    The alpha 4/beta 1 integrin very late antigen-4 (CD49d/CD29) is up-regulated on circulating neutrophils of septic patients...
  49. Langhauser F, Kraft P, Göb E, Leinweber J, Schuhmann M, Lorenz K, et al. Blocking of ?4 integrin does not protect from acute ischemic stroke in mice. Stroke. 2014;45:1799-806 pubmed publisher
    ..Animals treated with a monoclonal anti-CD49d antibody (300 ?g) 24 hours before or 3 hours after the onset of cerebral ischemia and stroke outcome, including ..
  50. Borchers M, Crosby J, Justice P, Farmer S, Hines E, Lee J, et al. Intrinsic AHR in IL-5 transgenic mice is dependent on CD4(+) cells and CD49d-mediated signaling. Am J Physiol Lung Cell Mol Physiol. 2001;281:L653-9 pubmed
    ..alpha(4)-integrin signaling to the development of AHR in IL-5 transgenic mice through the administration of anti-CD49d (alpha(4)-integrin) antibody (PS/2). Administration of PS/2 resulted in immediate (16-h) inhibition of AHR...
  51. Klemke M, Weschenfelder T, Konstandin M, Samstag Y. High affinity interaction of integrin alpha4beta1 (VLA-4) and vascular cell adhesion molecule 1 (VCAM-1) enhances migration of human melanoma cells across activated endothelial cell layers. J Cell Physiol. 2007;212:368-74 pubmed
    ..These data imply that only high affinity interactions between the integrin alpha4beta1 on melanoma cells and VCAM-1 on activated endothelial cells may enhance the metastatic capacity of human beta2/beta3-negative melanoma cells. ..
  52. Li B, Niu B, Chen L, Wei Z, Huang T, Jiang M, et al. Identifying chemicals with potential therapy of HIV based on protein-protein and protein-chemical interaction network. PLoS ONE. 2013;8:e65207 pubmed publisher
    ..All these indicate that our method as presented in this paper is quite promising. The method may become a useful tool, or at least plays a complementary role to the existing method, for identifying novel anti-HIV drugs. ..
  53. Weitkamp J, Kallewaard N, Bowen A, Lafleur B, Greenberg H, Crowe J. VH1-46 is the dominant immunoglobulin heavy chain gene segment in rotavirus-specific memory B cells expressing the intestinal homing receptor alpha4beta7. J Immunol. 2005;174:3454-60 pubmed
    ..Interestingly, RV-specific intestinal homing IgD-/alpha4beta7+ B cells using the VH1-46 gene segment were not mutated, in contrast to systemic RV-specific IgD- B cells. ..
  54. Woods Ignatoski K, Grewal N, Markwart S, Livant D, Ethier S. p38MAPK induces cell surface alpha4 integrin downregulation to facilitate erbB-2-mediated invasion. Neoplasia. 2003;5:128-34 pubmed
    ..These data strengthen the model where loss of alpha(4) integrin at the cell surface, leading to reduced alpha(4) integrin binding to plasma fibronectin, plays a role in erbB-2-mediated invasiveness. ..
  55. Gandoglia I, Ivaldi F, Carrega P, Armentani E, Ferlazzo G, Mancardi G, et al. In vitro VLA-4 blockade results in an impaired NK cell-mediated immune surveillance against melanoma. Immunol Lett. 2017;181:109-115 pubmed publisher
    Natalizumab (NTZ) is a monoclonal antibody targeting the α4β1 integrin (CD49d/CD29), very late antigen-4 (VLA-4), which is approved for treatment of relapsing-remitting multiple sclerosis (RR-MS)...
  56. Sonnenberg A, Linders C, Modderman P, Damsky C, Aumailley M, Timpl R. Integrin recognition of different cell-binding fragments of laminin (P1, E3, E8) and evidence that alpha 6 beta 1 but not alpha 6 beta 4 functions as a major receptor for fragment E8. J Cell Biol. 1990;110:2145-55 pubmed
    ..Adhesion to E3 may also be brought about by other receptor molecules, possibly proteoglycans, not belonging to the integrin family. ..
  57. Lu X, Li Z, Li Q, Jiao Y, Ji Y, Zhang H, et al. Preferential loss of gut-homing ?4?7 CD4+ T cells and their circulating functional subsets in acute HIV-1 infection. Cell Mol Immunol. 2016;13:776-784 pubmed publisher
  58. Slattery M, Mullany L, Sakoda L, Wolff R, Stevens J, Samowitz W, et al. The PI3K/AKT signaling pathway: Associations of miRNAs with dysregulated gene expression in colorectal cancer. Mol Carcinog. 2017;: pubmed publisher
    ..Other miRNA:mRNA associations with similar impact on the pathway were miR-203a with ITGA4, miR-6071 with ITGAV, and miR-375 with THBS2, all genes involved in extracellular matrix function that activate ..
  59. Liu J, Fu T, Peng B, Sun H, Chu H, Li G, et al. The hydrophobic contacts between the center of the ?I domain and the ?1/?7 helices are crucial for the low-affinity state of integrin ?4 ?7. FEBS J. 2014;281:2915-26 pubmed publisher
    ..Disruption of the hydrophobic contacts also induced the active conformation of ?4 ?7 . Thus, the findings obtained in the present study reveal an important structural basis for the low-affinity state of integrin. ..
  60. Noborio Hatano K, Kikuchi J, Takatoku M, Shimizu R, Wada T, Ueda M, et al. Bortezomib overcomes cell-adhesion-mediated drug resistance through downregulation of VLA-4 expression in multiple myeloma. Oncogene. 2009;28:231-42 pubmed publisher
    ..lines (KHM-1B, KMS12-BM, RPMI8226 and U266) and primary myeloma cells, we identified CD29 (beta1-integrin), CD44, CD49d (alpha4-integrin, a subunit of VLA-4), CD54 (intercellular adhesion molecule-1 (ICAM-1)), CD138 (syndecan-1) and ..
  61. Crook M, Southgate K, Newby A. Both ICAM-1- and VCAM-1-integrin interactions are important in mediating monocyte adhesion to human saphenous vein. J Vasc Res. 2002;39:221-9 pubmed
    ..These experiments imply that either integrin might be targeted to reduce monocyte infiltration into HSV grafts. ..
  62. Ruiz Velasco N, Guerrero Esteo M, Briskin M, Teixido J. The alpha(4) integrin subunit Tyr(187) has a key role in alpha(4)beta(7)-dependent cell adhesion. J Biol Chem. 2000;275:7052-9 pubmed
  63. Lv X, Liu B, Li X, Wang X, Li X, Ahmed N, et al. Integrin α4 Induces Lymphangiogenesis and Metastasis via Upregulation of VEGF-C in Human Colon Cancer. Anat Rec (Hoboken). 2016;299:741-7 pubmed publisher
    ..Our results demonstrated that integrin α4 is a novel prognostic indicator for human colon cancer. Anat Rec, 299:741-747, 2016. © 2016 Wiley Periodicals, Inc. ..
  64. Rubio M, Nueda A, Vara A, Corbí Lopez A. A single mRNA encodes the alpha 150 and alpha 80/70 forms of the alpha subunit of VLA4. Eur J Immunol. 1992;22:1099-102 pubmed
    VLA4 is a cell surface heterodimer (alpha 4 beta 1, CD49d/CD29) which belongs to the integrin family and is involved in cell-extracellular matrix interactions, as well as in intercellular adhesion...
  65. Liu C, LeClair P, Monajemi M, Sly L, Reid G, Lim C. α-Integrin expression and function modulates presentation of cell surface calreticulin. Cell Death Dis. 2016;7:e2268 pubmed publisher
    ..This study reveals a previously uncharacterized function of integrins as negative regulators of ICD by suppressing presentation of cell surface calreticulin. ..
  66. Bazan Socha S, Zuk J, Jakieła B, Pulka G, Pełka K, Musiał J. Increased expression of ?? (CD49b), ?? (CD49d) and ?? (CD29) integrin subunits on peripheral blood T lymphocytes in clinically stable mild-to-moderate persistent asthma. Pol Arch Med Wewn. 2012;122:585-90 pubmed
    ..The biological role of ?? subunit on T cells remains to be elucidated. ..
  67. Matsunaga T, Fukai F, Kameda T, Shide K, Shimoda H, Torii E, et al. Potentiated activation of VLA-4 and VLA-5 accelerates proplatelet-like formation. Ann Hematol. 2012;91:1633-43 pubmed publisher
    ..Thus, the enhanced activation of ERK1/2 by FN, PMA plus TNIIIA2 was responsible for acceleration of PPF with FN plus PMA...
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    ..Importantly, we found that the replacement of Arg168 by Ala (R168A mutant) induces the augmentation of cell migration via alpha4 and alpha9 integrins. ..
  69. Choi J, Lim S, Yoo Y, Jung J, Park J, Kim G. Microenvironmental Interaction Between Hypoxia and Endothelial Cells Controls the Migration Ability of Placenta-Derived Mesenchymal Stem Cells via α4 Integrin and Rho Signaling. J Cell Biochem. 2016;117:1145-57 pubmed publisher
    ..The findings suggest microenvironment event by hypoxia and the interaction with endothelial cells may be useful as a regulator of MSC migration and provide insight into the migratory mechanism of MSCs in stem cell-based therapy. ..
  70. Miles A, Liaskou E, Eksteen B, Lalor P, Adams D. CCL25 and CCL28 promote alpha4 beta7-integrin-dependent adhesion of lymphocytes to MAdCAM-1 under shear flow. Am J Physiol Gastrointest Liver Physiol. 2008;294:G1257-67 pubmed publisher
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    ..These results suggest a potential role for the lymphocyte ADAM, MDC-L, in the interaction of lymphocytes with alpha(4)beta(1)-expressing leukocytes. ..
  72. Quaranta M, Spinello I, Testa U, Mariani G, Diverio D, Foa R, et al. PLZF-mediated control on VLA-4 expression in normal and leukemic myeloid cells. Oncogene. 2006;25:399-408 pubmed
    ..However, in primary AMLs the control of PLZF on VLA-4 expression is lost. Altogether, we suggest that VLA-4 modulation by PLZF may represent an important step in the control of normal and leukemic cell mobilization. ..
  73. Savino W, Pinto Mariz F, Mouly V. Flow Cytometry-Defined CD49d Expression in Circulating T-Lymphocytes Is a Biomarker for Disease Progression in Duchenne Muscular Dystrophy. Methods Mol Biol. 2018;1687:219-227 pubmed publisher
    ..We recently showed that CD49d expression levels in blood-derived T-cell subsets can predict disease progression in DMD patients...