Gene Symbol: Itga4
Description: integrin alpha 4
Alias: CD49D, Itga4B, integrin alpha-4, CD49 antigen-like family member D, LPAM subunit alpha, VLA-4 receptor, alpha 4 subunit, VLA-4 subunit alpha, integrin alpha-IV, integrin alpha4B, lymphocyte Peyer patch adhesion molecules subunit alpha
Species: mouse
Products:     Itga4

Top Publications

  1. Kil S, Krull C, Cann G, Clegg D, Bronner Fraser M. The alpha4 subunit of integrin is important for neural crest cell migration. Dev Biol. 1998;202:29-42 pubmed
    ..Furthermore, the integrin alpha4 subunit represents a useful neural crest marker in the mouse. ..
  2. Arroyo A, Yang J, Rayburn H, Hynes R. Alpha4 integrins regulate the proliferation/differentiation balance of multilineage hematopoietic progenitors in vivo. Immunity. 1999;11:555-66 pubmed
    ..In summary, alpha4 integrins are essential for normal development of all hematopoietic lineages in fetal liver, bone marrow, and spleen, likely by regulating the proliferation/differentiation balance of hematopoietic progenitors. ..
  3. Basak S, Dhar R, Das C. Steroids modulate the expression of alpha4 integrin in mouse blastocysts and uterus during implantation. Biol Reprod. 2002;66:1784-9 pubmed
    ..Furthermore, the results also indicate the direct role of alpha4 integrin in the process of implantation. ..
  4. Hunter P, Swanson B, Haendel M, Lyons G, Cross J. Mrj encodes a DnaJ-related co-chaperone that is essential for murine placental development. Development. 1999;126:1247-58 pubmed
    ..The specificity of the developmental defect in Mrj mutants suggests that each of these genes may have unique tissue and cellular activities. ..
  5. Kerfoot S, Norman M, Lapointe B, Bonder C, Zbytnuik L, Kubes P. Reevaluation of P-selectin and alpha 4 integrin as targets for the treatment of experimental autoimmune encephalomyelitis. J Immunol. 2006;176:6225-34 pubmed
    ..Importantly, combined blockade of both adhesion molecules resulted in significantly better clinical outcome than anti-alpha(4) integrin alone. ..
  6. Katayama Y, Hidalgo A, Peired A, Frenette P. Integrin alpha4beta7 and its counterreceptor MAdCAM-1 contribute to hematopoietic progenitor recruitment into bone marrow following transplantation. Blood. 2004;104:2020-6 pubmed
    ..Although there may be other alpha4beta7 integrin ligands involved (eg, fibronectin and VCAM-1), these data thus suggest that alpha4beta7 and its counterreceptor MAdCAM-1 represent a novel adhesion pathway mediating HPC homing to BM. ..
  7. Schmid M, Avraamides C, Foubert P, Shaked Y, Kang S, Kerbel R, et al. Combined blockade of integrin-?4?1 plus cytokines SDF-1? or IL-1? potently inhibits tumor inflammation and growth. Cancer Res. 2011;71:6965-75 pubmed publisher
    ..These results show that targeting myeloid cell recruitment mechanisms can be an effective approach to suppress tumor progression. ..
  8. Pinco K, Liu S, Yang J. alpha4 integrin is expressed in a subset of cranial neural crest cells and in epicardial progenitor cells during early mouse development. Mech Dev. 2001;100:99-103 pubmed
    ..alpha 4 is also expressed in epicardial progenitor cells in the septum transversum that migrate to the heart. ..
  9. Kummer C, Petrich B, Rose D, Ginsberg M. A small molecule that inhibits the interaction of paxillin and alpha 4 integrin inhibits accumulation of mononuclear leukocytes at a site of inflammation. J Biol Chem. 2010;285:9462-9 pubmed publisher
    ..40,000-compound) chemical library, we identified a noncytotoxic inhibitor of this interaction that impaired integrin alpha 4-mediated but not alpha L beta 2-mediated Jurkat T cell migration...

More Information


  1. Yang J, Rayburn H, Hynes R. Cell adhesion events mediated by alpha 4 integrins are essential in placental and cardiac development. Development. 1995;121:549-60 pubmed
    ..These results raise the possibility of abortifacients targeting alpha 4 integrins, and raise serious questions about potential side effects of drugs currently being designed to block alpha 4 integrin functions in inflammation. ..
  2. Parr B, Cornish V, Cybulsky M, McMahon A. Wnt7b regulates placental development in mice. Dev Biol. 2001;237:324-32 pubmed
    ..Wnt7b also is required for normal organization of cells in the chorionic plate. Thus, Wnt7b signaling is central to the early stages of placental development in mammals. ..
  3. Rivera Rosado L, Horn T, McGrath S, Cotter R, Yang J. Association between ?4 integrin cytoplasmic tail and non-muscle myosin IIA regulates cell migration. J Cell Sci. 2011;124:483-92 pubmed publisher
    ..These results provide a new mechanism for linking integrins to the actomyosin cytoskeleton and for regulating cell migration by integrins and non-muscle myosin II. ..
  4. Feral C, Rose D, Han J, Fox N, Silverman G, Kaushansky K, et al. Blocking the alpha 4 integrin-paxillin interaction selectively impairs mononuclear leukocyte recruitment to an inflammatory site. J Clin Invest. 2006;116:715-23 pubmed
    ..We conclude that interference with alpha4 integrin signaling can selectively impair mononuclear leukocyte recruitment to sites of inflammation while sparing vital functions of alpha4 integrins in development and hematopoiesis. ..
  5. Gurtner G, Davis V, Li H, McCoy M, Sharpe A, Cybulsky M. Targeted disruption of the murine VCAM1 gene: essential role of VCAM-1 in chorioallantoic fusion and placentation. Genes Dev. 1995;9:1-14 pubmed
    ..They became viable and fertile adult mice with lack of VCAM-1 expression, normal organs, and an elevated number of circulating blood mononuclear leukocytes...
  6. Lu T, Cyster J. Integrin-mediated long-term B cell retention in the splenic marginal zone. Science. 2002;297:409-12 pubmed
    ..These studies identify key requirements for MZ B cell localization and establish a role for integrins in peripheral lymphoid tissue compartmentalization. ..
  7. Kwee L, Baldwin H, Shen H, Stewart C, Buck C, Buck C, et al. Defective development of the embryonic and extraembryonic circulatory systems in vascular cell adhesion molecule (VCAM-1) deficient mice. Development. 1995;121:489-503 pubmed
    ..These data suggest important roles for VCAM-1 and alpha 4 in the development of the placenta and the heart. ..
  8. Arroyo A, Yang J, Rayburn H, Hynes R. Differential requirements for alpha4 integrins during fetal and adult hematopoiesis. Cell. 1996;85:997-1008 pubmed
    ..We also show that alpha4 integrins are essential for T cell homing to Peyer's patches, but not to other secondary lymphoid organs, including spleen, lymph nodes, and intestinal epithelium. ..
  9. Tarone G, Russo M, Hirsch E, Odorisio T, Altruda F, Silengo L, et al. Expression of beta 1 integrin complexes on the surface of unfertilized mouse oocyte. Development. 1993;117:1369-75 pubmed
    ..These data demonstrate for the first time the expression of three beta 1 integrin complexes in unfertilized mouse oocytes. Such proteins may have a role in sperm-egg interaction or during very early steps of embryogenesis. ..
  10. Grazioli A, Alves C, Konstantopoulos K, Yang J. Defective blood vessel development and pericyte/pvSMC distribution in alpha 4 integrin-deficient mouse embryos. Dev Biol. 2006;293:165-77 pubmed
  11. Schmid M, Avraamides C, Dippold H, Franco I, Foubert P, Ellies L, et al. Receptor tyrosine kinases and TLR/IL1Rs unexpectedly activate myeloid cell PI3k?, a single convergent point promoting tumor inflammation and progression. Cancer Cell. 2011;19:715-27 pubmed publisher
    ..Pharmacological or genetic blockade of p110? suppressed inflammation, growth, and metastasis of implanted and spontaneous tumors, revealing an important therapeutic target in oncology. ..
  12. Lobb R, Hemler M. The pathophysiologic role of alpha 4 integrins in vivo. J Clin Invest. 1994;94:1722-8 pubmed
  13. Schultz J, Mayernik L, Rout U, Armant D. Integrin trafficking regulates adhesion to fibronectin during differentiation of mouse peri-implantation blastocysts. Dev Genet. 1997;21:31-43 pubmed
    ..Trafficking of alpha 5 beta 1, and possibly other integrins, to the apical surface of trophoblast cells appears to be a critical step in the differentiation of the mouse blastocyst to an invasive phenotype. ..
  14. Scott L, Priestley G, Papayannopoulou T. Deletion of alpha4 integrins from adult hematopoietic cells reveals roles in homeostasis, regeneration, and homing. Mol Cell Biol. 2003;23:9349-60 pubmed
  15. Lim C, Han J, Yousefi N, Ma Y, Amieux P, McKnight G, et al. Alpha4 integrins are type I cAMP-dependent protein kinase-anchoring proteins. Nat Cell Biol. 2007;9:415-21 pubmed
  16. Sengbusch J, He W, Pinco K, Yang J. Dual functions of [alpha]4[beta]1 integrin in epicardial development: initial migration and long-term attachment. J Cell Biol. 2002;157:873-82 pubmed
    ..T., H. Rayburn, and R.O. Hynes. 1995. Development. 121:549-560). ..
  17. Takahashi S, Leiss M, Moser M, Ohashi T, Kitao T, Heckmann D, et al. The RGD motif in fibronectin is essential for development but dispensable for fibril assembly. J Cell Biol. 2007;178:167-78 pubmed
    ..Our findings demonstrate that FN contains a novel motif for integrin binding and fibril formation whose activity is controlled by amino acid modification. ..
  18. Katayama Y, Hidalgo A, Furie B, Vestweber D, Furie B, Frenette P. PSGL-1 participates in E-selectin-mediated progenitor homing to bone marrow: evidence for cooperation between E-selectin ligands and alpha4 integrin. Blood. 2003;102:2060-7 pubmed
    ..Our results thus underscore a major difference between mature myeloid cells and immature stem/progenitor cells in that E-selectin ligands cooperate with alpha4 integrin rather than P-selectin ligands. ..
  19. Jaspers M, Wu R, Van Der Schueren B, Cassiman J. Localization of alpha 4m integrin at sites of mesenchyme condensation during embryonic mouse development. Differentiation. 1995;59:79-86 pubmed
    ..We also confirm that VCAM-1 and alpha 4 beta 1 are co-distributed only in some tissues, suggesting that during mouse development, VLA-4 interacts mainly with another ligand, probably fibronectin. ..
  20. Buck C, Edelman J, Buck C, Kennedy G, Baldwin H. Expression patterns of adhesion receptors in the developing mouse lung: functional implications. Cell Adhes Commun. 1996;4:69-87 pubmed
    ..The expression of thrombomodulin only at sites of airway branching suggests that the thrombin/thrombomodulin system could play a pivotal, regulatory role in branching morphogenesis. ..
  21. Sasaki K, Zhu X, Vasquez C, Nishimura F, Dusak J, Huang J, et al. Preferential expression of very late antigen-4 on type 1 CTL cells plays a critical role in trafficking into central nervous system tumors. Cancer Res. 2007;67:6451-8 pubmed
    ..of a panel of homing receptors on Tc1 and Tc2 cells, we found that very late antigen (VLA)-4 (a heterodimer of CD49d and CD29), but none of other receptors evaluated, was expressed at significantly higher levels on Tc1 cells than ..
  22. Banerjee E, Jiang Y, Henderson W, Scott L, Papayannopoulou T. Alpha4 and beta2 integrins have nonredundant roles for asthma development, but for optimal allergen sensitization only alpha4 is critical. Exp Hematol. 2007;35:605-17 pubmed
    ..As VCAM-1 deficiency did not protect mice from asthma, interactions of alpha4beta1(+) or alpha4beta7(+) cells with other ligands are suggested. ..
  23. Ring C, Ginsberg M, Haling J, Pendergast A. Abl-interactor-1 (Abi1) has a role in cardiovascular and placental development and is a binding partner of the alpha4 integrin. Proc Natl Acad Sci U S A. 2011;108:149-54 pubmed publisher
    ..The Abi1-?4 interaction establishes a mechanistic paradigm for signaling between adhesion events and enhanced actin polymerization at the earliest stages of protrusion. ..
  24. Gaspar Elsas M, Queto T, Vasconcelos Z, Jones C, Lannes Vieira J, Xavier Elsas P. Evidence for a regulatory role of alpha 4-integrins in the maturation of eosinophils generated from the bone marrow in the presence of dexamethasone. Clin Exp Allergy. 2009;39:1187-98 pubmed publisher
    ..In addition, increased alpha 4 expression following glucocorticoid exposure may contribute to the retention and accumulation of eosinophils in haemopoietic tissue. ..
  25. Sharma B, Ho L, Ford G, Chen H, Goldstone A, Woo Y, et al. Alternative Progenitor Cells Compensate to Rebuild the Coronary Vasculature in Elabela- and Apj-Deficient Hearts. Dev Cell. 2017;42:655-666.e3 pubmed publisher
    ..Our data demonstrate that by diversifying their responsivity to growth cues, distinct coronary progenitor pools are able to compensate for each other during coronary development, thereby providing robustness to organ development. ..
  26. Behrends J, Karsten C, Wilke S, Röbke A, Kruse A. Identification of ITGA4/ITGB7 and ITGAE/ITGB7 expressing subsets of decidual dendritic-like cells within distinct microdomains of the pregnant mouse uterus. Biol Reprod. 2008;79:624-32 pubmed publisher
    ..analysis we demonstrated the existence of three distinct DC subsets, characterized by differential expression of ITGA4/ITGB7 (formerly alpha4beta7-integrin) and ITGAE/ITGB7 (formerly alphaEbeta7-integrin)...
  27. Wang C, McDonough J, McDonald K, Huang C, Newberry R. Alpha4beta7/MAdCAM-1 interactions play an essential role in transitioning cryptopatches into isolated lymphoid follicles and a nonessential role in cryptopatch formation. J Immunol. 2008;181:4052-61 pubmed
  28. Chan C, Weeber E, Kurup S, Sweatt J, Davis R. Integrin requirement for hippocampal synaptic plasticity and spatial memory. J Neurosci. 2003;23:7107-16 pubmed
    ..These results demonstrate that several different integrins are involved in physiological plasticity and provide the first evidence of their requirement for behavioral plasticity in vertebrates. ..
  29. Shu F, Holzmann B, Seibold F, Erle D, Kearney J. Activated alpha4 integrins are preferentially expressed on immature thymocytes and activated T cells. Dev Immunol. 2002;9:73-84 pubmed
    ..These results suggest that the activation of the alpha4 integrins is parallel to that of T cells. ..
  30. Rothhammer V, Heink S, Petermann F, Srivastava R, Claussen M, Hemmer B, et al. Th17 lymphocytes traffic to the central nervous system independently of ?4 integrin expression during EAE. J Exp Med. 2011;208:2465-76 pubmed publisher
    ..These observations have implications for the understanding of lesion localization, immunosurveillance, and drug design in multiple sclerosis. ..
  31. Hsieh Y, Gang E, Geng H, Park E, Huantes S, Chudziak D, et al. Integrin alpha4 blockade sensitizes drug resistant pre-B acute lymphoblastic leukemia to chemotherapy. Blood. 2013;121:1814-8 pubmed publisher
    ..Chemotherapy combined with Natalizumab prolonged survival of NOD/SCID recipients of primary ALL, suggesting adjuvant alpha4 inhibition as a novel strategy for pre-B ALL. ..
  32. Bonato V, Goncalves E, Santos R, Silva C. Genetic aspects and microenvironment affect expression of CD18 and VLA-4 in experimental tuberculosis. Scand J Immunol. 2002;56:185-94 pubmed
    ..Thus, the up- or downmodulation of these adhesion receptors is probably associated with differential recruitment of T cells at the site of infection, which may or may not mediate protection in experimental tuberculosis...
  33. Shibata M, GARCIA GARCIA M. The mouse KRAB zinc-finger protein CHATO is required in embryonic-derived tissues to control yolk sac and placenta morphogenesis. Dev Biol. 2011;349:331-41 pubmed publisher
    ..Our results support previously undescribed roles of the extraembryonic mesoderm in yolk sac morphogenesis and in the closure of the ectoplacental cavity and identify a novel role of ZFP568 in the development of extraembryonic tissues...
  34. Ripich T, Jessberger R. SWAP-70 regulates erythropoiesis by controlling ?4 integrin. Haematologica. 2011;96:1743-52 pubmed publisher
    ..Integrin-dependent adhesion plays important roles in erythropoiesis, but how integrins are regulated during erythropoiesis remains largely unknown...
  35. Ringelmann B, Roder C, Hallmann R, Maley M, Davies M, Grounds M, et al. Expression of laminin alpha1, alpha2, alpha4, and alpha5 chains, fibronectin, and tenascin-C in skeletal muscle of dystrophic 129ReJ dy/dy mice. Exp Cell Res. 1999;246:165-82 pubmed
    ..These results have significant ramifications in the diagnosis of human merosin-negative CMD. ..
  36. Zhi K, Li M, Zhang X, Gao Z, Bai J, Wu Y, et al. ?4?7 Integrin (LPAM-1) is upregulated at atherosclerotic lesions and is involved in atherosclerosis progression. Cell Physiol Biochem. 2014;33:1876-87 pubmed publisher
    ..Together our results reveal a critical role of ?4?7 in diet-induced atherosclerosis in mouse. ..
  37. Glatigny S, Duhen R, Oukka M, Bettelli E. Cutting edge: loss of ?4 integrin expression differentially affects the homing of Th1 and Th17 cells. J Immunol. 2011;187:6176-9 pubmed publisher
    ..Therefore, our data suggest that anti-?4 integrin Ab treatment may be more efficient in the treatment of Th1- rather than Th17-mediated disease. ..
  38. Chen S, Chen M, Wang X, Zhang J, Wen Q, Ji S, et al. The Wilms tumor gene, Wt1, maintains testicular cord integrity by regulating the expression of Col4a1 and Col4a2. Biol Reprod. 2013;88:56 pubmed publisher
  39. Schippers A, Muschaweck M, Clahsen T, Tautorat S, Grieb L, Tenbrock K, et al. β7-Integrin exacerbates experimental DSS-induced colitis in mice by directing inflammatory monocytes into the colon. Mucosal Immunol. 2016;9:527-38 pubmed publisher
    ..In summary, we demonstrate a previously unknown role of α4β7-integrin-MAdCAM-1 interactions as drivers of colitis by directing inflammatory monocytes into the colon. ..
  40. van Nes J, de Graaff W, Lebrin F, Gerhard M, Beck F, Deschamps J. The Cdx4 mutation affects axial development and reveals an essential role of Cdx genes in the ontogenesis of the placental labyrinth in mice. Development. 2006;133:419-28 pubmed
    ..Cdx genes thus operate in a redundant way during placentogenesis, as they do during embryonic axial elongation and patterning, and independently from the previously reported early Cdx2-specific role in the trophectoderm at implantation...
  41. 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
  42. Papadaki C, Alexiou M, Cecena G, Verykokakis M, Bilitou A, Cross J, et al. Transcriptional repressor erf determines extraembryonic ectoderm differentiation. Mol Cell Biol. 2007;27:5201-13 pubmed
    ..Our data suggest that attenuation of FGF/Erk signaling and consecutive Erf nuclear localization and function is required for extraembryonic ectoderm differentiation, ectoplacental cone cavity closure, and chorioallantoic attachment. ..
  43. Kim D, Morii E, Ogihara H, Hashimoto K, Oritani K, Lee Y, et al. Impaired expression of integrin alpha-4 subunit in cultured mast cells derived from mutant mice of mi/mi genotype. Blood. 1998;92:1973-80 pubmed
    ..The deletion or mutation of the CACTTG motif abolished the transactivation by +-MITF, suggesting that +-MITF directly transactivated the gene encoding alpha4 subunit of integrin. ..
  44. Yang J, Rando T, Mohler W, Rayburn H, Blau H, Hynes R. Genetic analysis of alpha 4 integrin functions in the development of mouse skeletal muscle. J Cell Biol. 1996;135:829-35 pubmed
    ..Taking these results together, we conclude that alpha 4 integrins appear not to play essential roles in normal skeletal muscle development. ..
  45. Sheppard A, Onken M, Rosen G, Noakes P, Dean D. Expanding roles for alpha 4 integrin and its ligands in development. Cell Adhes Commun. 1994;2:27-43 pubmed
    ..Finally, based on their patterns of expression, we conclude that VCAM-1 only participates in a subset of interactions involving alpha 4 integrins, whereas FN appears to be the more general ligand. ..
  46. Henderson W, Chi E, Albert R, Chu S, Lamm W, Rochon Y, et al. Blockade of CD49d (alpha4 integrin) on intrapulmonary but not circulating leukocytes inhibits airway inflammation and hyperresponsiveness in a mouse model of asthma. J Clin Invest. 1997;100:3083-92 pubmed
    ..allergic pulmonary inflammation in ovalbumin-sensitized mice was used to address the role of the alpha4 integrin (CD49d) in mediating the airway inflammation and hyperresponsiveness...
  47. Kim S, Xiang W, Kwak C, Yang Y, Lin X, Ota M, et al. GPR15-mediated homing controls immune homeostasis in the large intestine mucosa. Science. 2013;340:1456-9 pubmed publisher
    ..Our findings thus describe a T cell-homing receptor for LILP and indicate that GPR15 plays a role in mucosal immune tolerance largely by regulating the influx of Tregs. ..
  48. Yu Y, Schürpf T, Springer T. How natalizumab binds and antagonizes ?4 integrins. J Biol Chem. 2013;288:32314-25 pubmed publisher
    ..Skewing away from these conserved regions of the epitopes recognized by current therapeutic function-blocking antibodies has resulted in previously unanticipated mechanisms of action. ..
  49. Zhang H, Zheng Y, Pan Y, Xie C, Sun H, Zhang Y, et al. Regulatory T-cell depletion in the gut caused by integrin β7 deficiency exacerbates DSS colitis by evoking aberrant innate immunity. Mucosal Immunol. 2016;9:391-400 pubmed publisher
    ..Thus, integrin α4β7 is essential for suppression of DSS colitis as it regulates the colonic Treg cell population and innate immunity. ..
  50. Schollen E, de Meirsman C, Matthijs G, Cassiman J. A regulatory element in the 5'UTR directs cell-specific expression of the mouse alpha 4 gene. Biochem Biophys Res Commun. 1995;211:115-22 pubmed
    ..Thus both ubiquitous and cell type-specific factors regulate the expression of alpha 4m. ..
  51. Martin Blondel G, Pignolet B, Tietz S, Yshii L, Gebauer C, Périnat T, et al. Migration of encephalitogenic CD8 T cells into the central nervous system is dependent on the α4β1-integrin. Eur J Immunol. 2015;45:3302-12 pubmed publisher
    ..In addition, inhibition of junctional adhesion molecule-B expressed by CNS endothelial cells also decreases CD8 T-cell infiltration. CD8 T cells may use additional and possibly unidentified adhesion molecules to gain access to the CNS. ..
  52. Stagg A, Kamm M, Knight S. Intestinal dendritic cells increase T cell expression of alpha4beta7 integrin. Eur J Immunol. 2002;32:1445-54 pubmed
    ..Therefore, in addition to their other immunoregulatory roles, DC have the potential to shape immune responses by influencing the homing of the lymphocytes they activate. ..
  53. Aigner S, Ruppert M, Hubbe M, Sammar M, Sthoeger Z, Butcher E, et al. Heat stable antigen (mouse CD24) supports myeloid cell binding to endothelial and platelet P-selectin. Int Immunol. 1995;7:1557-65 pubmed
    ..Our data suggest that HSA, in addition to the recently identified 160 kDa glycoprotein ligand on mouse neutrophils, belongs to a group of monospecific P-selectin ligands on myeloid cells. ..