DX5

Summary

Gene Symbol: DX5
Description: integrin alpha 2
Alias: CD49B, DX5, GPIa, integrin alpha-2, CD49 antigen-like family member B, VLA-2 receptor, alpha 2 subunit, collagen receptor, platelet membrane glycoprotein Ia
Species: mouse
Products:     DX5

Top Publications

  1. Chen J, Diacovo T, Grenache D, Santoro S, Zutter M. The alpha(2) integrin subunit-deficient mouse: a multifaceted phenotype including defects of branching morphogenesis and hemostasis. Am J Pathol. 2002;161:337-44 pubmed
    ..The alpha(2)beta(1) integrin-null mouse thus exhibits diverse, sometimes subtle, phenotypes consistent with the widespread pattern of alpha(2)beta(1) integrin expression. ..
  2. Edelson B, Stricker T, Li Z, Dickeson S, Shepherd V, Santoro S, et al. Novel collectin/C1q receptor mediates mast cell activation and innate immunity. Blood. 2006;107:143-50 pubmed
    ..This finding suggests that the alpha2beta1 integrin is not only important for innate immunity but may serve as a critical target for the regulation of autoimmune/allergic disorders. ..
  3. Zhang Z, Bothe I, Hirche F, Zweers M, Gullberg D, Pfitzer G, et al. Interactions of primary fibroblasts and keratinocytes with extracellular matrix proteins: contribution of alpha2beta1 integrin. J Cell Sci. 2006;119:1886-95 pubmed
    ..The deficits observed for alpha2-deficient fibroblasts appeared to be linked to alterations in the distribution of force-bearing focal adhesions and deregulation of Rho-GTPase activation. ..
  4. Ramirez N, Zhang Z, Madamanchi A, Boyd K, O Rear L, Nashabi A, et al. The ???? integrin is a metastasis suppressor in mouse models and human cancer. J Clin Invest. 2011;121:226-37 pubmed publisher
    ..Thus, the ?2?1 integrin functionally inhibits breast tumor metastasis, and ?2 expression may serve as an important biomarker of metastatic potential and patient survival. ..
  5. Marjoram R, Voss B, Pan Y, Dickeson S, Zutter M, Hamm H, et al. Suboptimal activation of protease-activated receptors enhances alpha2beta1 integrin-mediated platelet adhesion to collagen. J Biol Chem. 2009;284:34640-7 pubmed publisher
  6. Zou Z, Schmaier A, Cheng L, Mericko P, Dickeson S, Stricker T, et al. Negative regulation of activated alpha-2 integrins during thrombopoiesis. Blood. 2009;113:6428-39 pubmed publisher
  7. Hong Y, Lange Asschenfeldt B, Velasco P, Hirakawa S, Kunstfeld R, Brown L, et al. VEGF-A promotes tissue repair-associated lymphatic vessel formation via VEGFR-2 and the alpha1beta1 and alpha2beta1 integrins. FASEB J. 2004;18:1111-3 pubmed
  8. Edelson B, Li Z, Pappan L, Zutter M. Mast cell-mediated inflammatory responses require the alpha 2 beta 1 integrin. Blood. 2004;103:2214-20 pubmed
    ..We conclude that alpha 2 beta 1 integrin provides a costimulatory function required for mast cell activation and cytokine production in response to infection. ..
  9. Owens D, Watt F. Influence of beta1 integrins on epidermal squamous cell carcinoma formation in a transgenic mouse model: alpha3beta1, but not alpha2beta1, suppresses malignant conversion. Cancer Res. 2001;61:5248-54 pubmed
    ..Our results demonstrate that the alpha3beta1 integrin can suppress malignant conversion, and that the mechanism may involve CD81. ..

More Information

Publications62

  1. Sutherland A, Calarco P, Damsky C. Developmental regulation of integrin expression at the time of implantation in the mouse embryo. Development. 1993;119:1175-86 pubmed
    ..abstract truncated at 400 words) ..
  2. Zhang Z, Ramirez N, Yankeelov T, Li Z, Ford L, Qi Y, et al. alpha2beta1 integrin expression in the tumor microenvironment enhances tumor angiogenesis in a tumor cell-specific manner. Blood. 2008;111:1980-8 pubmed
    ..Thus integrin alpha2-null mice represent an example of genetic alterations of "the soil" determining response to the "seed." ..
  3. Chen H, Zou Z, Sarratt K, Zhou D, Zhang M, Sebzda E, et al. In vivo beta1 integrin function requires phosphorylation-independent regulation by cytoplasmic tyrosines. Genes Dev. 2006;20:927-32 pubmed
    ..These results have important implications for the molecular mechanism and regulation of integrin function. ..
  4. Cheli Y, Kunicki T. hnRNP L regulates differences in expression of mouse integrin alpha2beta1. Blood. 2006;107:4391-8 pubmed
    ..Thus, decreased surface alpha2beta1 results from decreased Itga2 pre-mRNA splicing regulated by hnRNP L and depends on CA repeat length at a specific site in intron 1. ..
  5. Sarratt K, Chen H, Zutter M, Santoro S, Hammer D, Kahn M. GPVI and alpha2beta1 play independent critical roles during platelet adhesion and aggregate formation to collagen under flow. Blood. 2005;106:1268-77 pubmed
    ..These studies establish platelet-collagen responses under physiologic flow as the consequence of a close partnership between 2 structurally distinct receptors and suggest that both receptors play significant hemostatic roles in vivo. ..
  6. He L, Pappan L, Grenache D, Li Z, Tollefsen D, Santoro S, et al. The contributions of the alpha 2 beta 1 integrin to vascular thrombosis in vivo. Blood. 2003;102:3652-7 pubmed
    ..Our results are the first to document a critical in vivo role for the alpha 2 beta 1 integrin in thrombus formation at the vessel wall under conditions of shear following vascular injury. ..
  7. Holtkötter O, Nieswandt B, Smyth N, Muller W, Hafner M, Schulte V, et al. Integrin alpha 2-deficient mice develop normally, are fertile, but display partially defective platelet interaction with collagen. J Biol Chem. 2002;277:10789-94 pubmed
    ..However, in the presence of an antibody against GPVI (activating platelet collagen receptor), adhesion of alpha(2)-deficient but not wild type platelets is abrogated...
  8. Rubel D, Frese J, Martin M, Leibnitz A, Girgert R, Miosge N, et al. Collagen receptors integrin alpha2beta1 and discoidin domain receptor 1 regulate maturation of the glomerular basement membrane and loss of integrin alpha2beta1 delays kidney fibrosis in COL4A3 knockout mice. Matrix Biol. 2014;34:13-21 pubmed publisher
    ..As demonstrated in the type IV collagen disease Alport syndrome, glomerular cell-matrix interactions via collagen receptors play an important role in the progression of renal fibrosis. ..
  9. Park S, Park H, Park C, Ko Y, Im E, Jo I, et al. Association of the gene polymorphisms of platelet glycoprotein Ia and IIb/IIIa with myocardial infarction and extent of coronary artery disease in the Korean population. Yonsei Med J. 2004;45:428-34 pubmed
    ..In this study, we investigated the role of GPIa, HPA-1 and HPA-3 polymorphisms as putative risk factors for myocardial infarction (MI) and the extent of coronary ..
  10. Roche F, Sipilä K, Honjo S, Johansson S, Tugues S, Heino J, et al. Histidine-rich glycoprotein blocks collagen-binding integrins and adhesion of endothelial cells through low-affinity interaction with α2 integrin. Matrix Biol. 2015;48:89-99 pubmed publisher
    ..We conclude that HRG binds to α2 integrin through low-affinity interactions in a HS-independent manner, thereby blocking EC-adhesion to COL I. ..
  11. Dong Z, Cruz Munoz M, Zhong M, Chen R, Latour S, Veillette A. Essential function for SAP family adaptors in the surveillance of hematopoietic cells by natural killer cells. Nat Immunol. 2009;10:973-80 pubmed publisher
    ..Hence, the SAP family is essential for the elimination of unwanted hematopoietic cells by NK cells. ..
  12. Barbour W, Saika S, Miyamoto T, Ohkawa K, Utsunomiya H, Ohnishi Y. Expression patterns of beta1-related alpha integrin subunits in murine lens during embryonic development and wound healing. Curr Eye Res. 2004;29:1-10 pubmed
  13. Stepp M. Alpha9 and beta8 integrin expression correlates with the merger of the developing mouse eyelids. Dev Dyn. 1999;214:216-28 pubmed
    ..The data presented identify specific integrins and matrix proteins that are likely to mediate eyelid fusion. ..
  14. Kassiotis G, Gray D, Kiafard Z, Zwirner J, Stockinger B. Functional specialization of memory Th cells revealed by expression of integrin CD49b. J Immunol. 2006;177:968-75 pubmed
    ..this study, we report the functional characterization of two memory Th subsets, defined by expression of integrin CD49b. Stable CD49b expression is induced in up to one-half of all memory Th cells...
  15. Madamanchi A, Capozzi M, Geng L, Li Z, Friedman R, Dickeson S, et al. Mitigation of oxygen-induced retinopathy in ?2?1 integrin-deficient mice. Invest Ophthalmol Vis Sci. 2014;55:4338-47 pubmed publisher
    ..Our data suggest that the ?2?1 integrin contributes to the pathogenesis of retinopathy. We describe a newly identified role for ?2?1 integrin in mediating hypoxia-induced Müller cell VEGF-A production. ..
  16. el Bannoudi H, Han W, Stoop J, Louis Plence P, Huizinga T, Toes R. DX5+ CD4+ T cells modulate CD4+ T-cell response via inhibition of IL-12 production by DCs. Eur J Immunol. 2013;43:439-46 pubmed publisher
    b>DX5(+) CD4(+) T cells have been shown to dampen collagen-induced arthritis and delayed-type hypersensitivity reactions in mice...
  17. Tigges U, Boroujerdi A, Welser Alves J, Milner R. TNF-? promotes cerebral pericyte remodeling in vitro, via a switch from ?1 to ?2 integrins. J Neuroinflammation. 2013;10:33 pubmed publisher
    ..These results thus define a fundamental molecular mechanism in which TNF-? stimulates pericyte remodeling in an ?2 integrin-dependent manner. ..
  18. Grenache D, Zhang Z, Wells L, Santoro S, Davidson J, Zutter M. Wound healing in the alpha2beta1 integrin-deficient mouse: altered keratinocyte biology and dysregulated matrix metalloproteinase expression. J Invest Dermatol. 2007;127:455-66 pubmed
  19. Cann G, Bradshaw A, Gervin D, Hunter A, Clegg D. Widespread expression of beta1 integrins in the developing chick retina: evidence for a role in migration of retinal ganglion cells. Dev Biol. 1996;180:82-96 pubmed
    ..RGC migration from the ventricular zone to the vitreal border was significantly inhibited, suggesting that beta1 integrins play a role in neuroblast migration in the retina. ..
  20. Romero M, Carroll J, Watt F. Analysis of cultured keratinocytes from a transgenic mouse model of psoriasis: effects of suprabasal integrin expression on keratinocyte adhesion, proliferation and terminal differentiation. Exp Dermatol. 1999;8:53-67 pubmed
  21. Suehiro K, Plow E. Ligand recognition by beta 3 integrins. Keio J Med. 1997;46:111-4 pubmed
    ..Since the beta 3 integrins have multiple functions in vivo and are targets for therapy, this classification system may be useful in the design and characterization of therapeutic agents. ..
  22. Wright S, Parham C, Lee B, Clarke D, Auckland L, Johnston J, et al. Perlecan domain V inhibits ?2 integrin-mediated amyloid-? neurotoxicity. Neurobiol Aging. 2012;33:1379-88 pubmed publisher
    ..We propose that domain V and potentially other ?2 integrin ligands could be a new therapeutic approach for inhibiting the A? plaque deposition and neurotoxicity observed in Alzheimer's disease. ..
  23. Schaff M, Receveur N, Bourdon C, Wurtz V, Denis C, Orend G, et al. Novel function of tenascin-C, a matrix protein relevant to atherosclerosis, in platelet recruitment and activation under flow. Arterioscler Thromb Vasc Biol. 2011;31:117-24 pubmed publisher
    ..This study provides evidence that TN-C serves as a novel adhesive matrix for platelets in a context that is relevant to atherothrombosis. ..
  24. Cailleteau L, Estrach S, Thyss R, Boyer L, Doye A, Domange B, et al. alpha2beta1 integrin controls association of Rac with the membrane and triggers quiescence of endothelial cells. J Cell Sci. 2010;123:2491-501 pubmed publisher
    ..Altogether, our data establish that alpha2beta1 integrin controls endothelial cell commitment towards quiescence by triggering a CD9-dependent dominant signaling. ..
  25. Schaff M, Receveur N, Bourdon C, Ohlmann P, Lanza F, Gachet C, et al. ?-arrestin-1 participates in thrombosis and regulates integrin aIIb?3 signalling without affecting P2Y receptors desensitisation and function. Thromb Haemost. 2012;107:735-48 pubmed publisher
  26. Hong J, Chu M, Qian L, Wang J, Guo Y, Xu D. Fibrillar Type I Collagen Enhances the Differentiation and Proliferation of Myofibroblasts by Lowering ?2?1 Integrin Expression in Cardiac Fibrosis. Biomed Res Int. 2017;2017:1790808 pubmed publisher
  27. Nikolova Krstevski V, Bhasin M, Otu H, Libermann T, Oettgen P. Gene expression analysis of embryonic stem cells expressing VE-cadherin (CD144) during endothelial differentiation. BMC Genomics. 2008;9:240 pubmed publisher
  28. McCall Culbreath K, Li Z, Zutter M. Crosstalk between the alpha2beta1 integrin and c-met/HGF-R regulates innate immunity. Blood. 2008;111:3562-70 pubmed publisher
    ..These findings suggest that crosstalk between c-met and the alpha2beta1 integrin may contribute to mast-cell activation in autoimmune and inflammatory disorders. ..
  29. Blumbach K, Niehoff A, Belgardt B, Ehlen H, Schmitz M, Hallinger R, et al. Dwarfism in mice lacking collagen-binding integrins ?2?1 and ?11?1 is caused by severely diminished IGF-1 levels. J Biol Chem. 2012;287:6431-40 pubmed publisher
    ..Thus, coupling hormone secretion to extracellular matrix signaling via integrins represents a novel concept in the control of endocrine homeostasis...
  30. Popova S, Rodriguez Sanchez B, Lidén A, Betsholtz C, Van Den Bos T, Gullberg D. The mesenchymal alpha11beta1 integrin attenuates PDGF-BB-stimulated chemotaxis of embryonic fibroblasts on collagens. Dev Biol. 2004;270:427-42 pubmed
    ..IV, V, and XI in response to PDGF-BB in vitro, whereas mutant fibroblasts that lacked alpha11beta1 in their collagen receptor repertoire showed a stronger chemotactic response on collagens when stimulated with PDGF-BB...
  31. Suh H, Han H. Collagen I regulates the self-renewal of mouse embryonic stem cells through ?2?1 integrin- and DDR1-dependent Bmi-1. J Cell Physiol. 2011;226:3422-32 pubmed publisher
    ..These results indicate that collagen I stimulates the self-renewal of mESCs mediated by Bmi-1 through ?2?1 integrin-dependent ILK, Notch, Gli-1, and DDR1-dependent Ras, PI3K/Akt, and ERK. ..
  32. Rossier O, Octeau V, Sibarita J, Leduc C, Tessier B, Nair D, et al. Integrins ?1 and ?3 exhibit distinct dynamic nanoscale organizations inside focal adhesions. Nat Cell Biol. 2012;14:1057-67 pubmed publisher
    ..Thus, differential transmission of actin motion to fibronectin occurs through specific integrins within FAs...
  33. Gardner H, Kreidberg J, Koteliansky V, Jaenisch R. Deletion of integrin alpha 1 by homologous recombination permits normal murine development but gives rise to a specific deficit in cell adhesion. Dev Biol. 1996;175:301-13 pubmed
    ..In the adult it is the sole collagen receptor in smooth muscle and liver and is thought to be important for the stability of these tissues...
  34. El Azreq M, Boisvert M, Cesaro A, Page N, Loubaki L, Allaeys I, et al. ?2?1 integrin regulates Th17 cell activity and its neutralization decreases the severity of collagen-induced arthritis. J Immunol. 2013;191:5941-50 pubmed publisher
  35. Yuan B, Li C, Kimura S, Engelhardt R, Smith B, Minoo P. Inhibition of distal lung morphogenesis in Nkx2.1(-/-) embryos. Dev Dyn. 2000;217:180-90 pubmed
    ..1 independent, while distal lung morphogenesis appears to be strictly dependent on the wild-type activity of Nkx2.1. ..
  36. Hughes C, Finney B, Koentgen F, Lowe K, Watson S. The N-terminal SH2 domain of Syk is required for (hem)ITAM, but not integrin, signaling in mouse platelets. Blood. 2015;125:144-54 pubmed publisher
    ..These results demonstrate that αIIbβ3 regulates Syk through an ITAM-independent pathway in mice and provide novel insight into the course of events underlying Syk activation and hemITAM phosphorylation by CLEC-2. ..
  37. Littlewood Evans A, Muller U. Stereocilia defects in the sensory hair cells of the inner ear in mice deficient in integrin alpha8beta1. Nat Genet. 2000;24:424-8 pubmed
    ..Mutations affecting matrix molecules cause inherited forms of inner ear disease and integrins may mediate some effects of matrix molecules in the ear; thus, mutations in integrin genes may lead to inner-ear diseases as well. ..
  38. Chaen T, Konno T, Egashira M, Bai R, Nomura N, Nomura S, et al. Estrogen-dependent uterine secretion of osteopontin activates blastocyst adhesion competence. PLoS ONE. 2012;7:e48933 pubmed publisher
    ..These findings define for the first time specific regulatory components of an estrogen-dependent pathway coordinating blastocyst adhesion competence and uterine receptivity...
  39. Carroll J, Luetteke N, Lee D, Watt F. Role of integrins in mouse eyelid development: studies in normal embryos and embryos in which there is a failure of eyelid fusion. Mech Dev. 1998;78:37-45 pubmed
    ..We speculate that selective and coordinated expression of the alpha5beta1 integrin and fibronectin in eyelid tip cells is required for eyelid fusion and may be under the control of growth factors that include TGF-alpha. ..
  40. Gagliani N, Magnani C, Huber S, Gianolini M, Pala M, Licona Limón P, et al. Coexpression of CD49b and LAG-3 identifies human and mouse T regulatory type 1 cells. Nat Med. 2013;19:739-46 pubmed publisher
    ..By gene expression profiling of human Tr1 cell clones, we identified the surface markers CD49b and lymphocyte activation gene 3 (LAG-3) as being stably and selectively coexpressed on mouse and human Tr1 cells...
  41. Uchio Yamada K, Manabe N, Yamaguchi M, Akashi N, Goto Y, Yamamoto Y, et al. Localization of extracellular matrix receptors in ICGN mice, a strain of mice with hereditary nephrotic syndrome. J Vet Med Sci. 2001;63:1171-8 pubmed
  42. Banerjee E, Jiang Y, Henderson W, Latchman Y, Papayannopoulou T. Absence of alpha 4 but not beta 2 integrins restrains development of chronic allergic asthma using mouse genetic models. Exp Hematol. 2009;37:715-727.e3 pubmed publisher
  43. Volpe M, Chung E, Ulm J, Gilchrist B, Ralston S, Wang K, et al. Aberrant cell adhesion molecule expression in human bronchopulmonary sequestration and congenital cystic adenomatoid malformation. Am J Physiol Lung Cell Mol Physiol. 2009;297:L143-52 pubmed publisher
    ..Aberrant cell adhesion molecule and Hox protein regulation are likely part of the mechanism involved in the development of BPS and CCAM...
  44. Li T, Larrucea S, Souza S, Leal S, Lopez J, Rubin E, et al. Genetic variation responsible for mouse strain differences in integrin alpha 2 expression is associated with altered platelet responses to collagen. Blood. 2004;103:3396-402 pubmed
    ..These strain differences serve as a useful model for the 2-fold difference in human platelet alpha(2)beta(1) expression and demonstrate that alpha(2)beta(1) participates in signaling during platelet activation. ..
  45. Chen P, Abacherli L, Nadler S, Wang Y, Li Q, Parks W. MMP7 shedding of syndecan-1 facilitates re-epithelialization by affecting alpha(2)beta(1) integrin activation. PLoS ONE. 2009;4:e6565 pubmed publisher
    ..MMP7 acts in the lungs to regulate inflammation and repair, and our data now show that both these functions are controlled through the shedding of syndecan-1. ..
  46. Wu J, Santoro S. Differential expression of integrin alpha subunits supports distinct roles during lung branching morphogenesis. Dev Dyn. 1996;206:169-81 pubmed
  47. Laplante P, Raymond M, Labelle A, Abe J, Iozzo R, Hébert M. Perlecan proteolysis induces an alpha2beta1 integrin- and Src family kinase-dependent anti-apoptotic pathway in fibroblasts in the absence of focal adhesion kinase activation. J Biol Chem. 2006;281:30383-92 pubmed
    ..In the long term, additional SFK members are recruited for sustaining the anti-apoptotic response, which could play crucial roles in abnormal fibrogenic healing. ..
  48. Nissinen L, Rappu P, Ollikka P, Nieminen J, Marjamäki A, Heino J. Platelet response to a small molecule inhibitor of α2β1 integrin is associated with ITGA2 C807T dimorphism. Platelets. 2016;27:378-80 pubmed publisher
    High expression of the collagen receptor, α2β1 integrin, on platelets of ITGA2 807T-allele carriers has been identified as a risk factor for thromboembolic conditions, and α2β1 inhibitors are considered to be potential ..
  49. Jarvis G, Bihan D, Hamaia S, Pugh N, Ghevaert C, Pearce A, et al. A role for adhesion and degranulation-promoting adapter protein in collagen-induced platelet activation mediated via integrin α(2) β(1). J Thromb Haemost. 2012;10:268-77 pubmed publisher
    ..In addition, we found that ADAP(-/-) mice, which are mildly thrombocytopenic, have enlarged spleens as compared with wild-type animals. This may reflect increased removal of platelets from the circulation. ..
  50. Banerjee A, Kim B, Carmona E, Cutting A, Gurney M, Carlos C, et al. Bacterial Pili exploit integrin machinery to promote immune activation and efficient blood-brain barrier penetration. Nat Commun. 2011;2:462 pubmed publisher
    ..Our results suggest that the bacterial pilus, specifically the PilA adhesin, has a dual role in immune activation and bacterial entry into the CNS. ..
  51. Sakthianandeswaren A, Christie M, D Andreti C, Tsui C, Jorissen R, Li S, et al. PHLDA1 expression marks the putative epithelial stem cells and contributes to intestinal tumorigenesis. Cancer Res. 2011;71:3709-19 pubmed publisher
    ..We conclude that PHLDA1 is a putative epithelial stem cell marker in the human small and large intestine and contributes to migration and proliferation in colon cancer cells. ..
  52. Edelman J, Chan B, Uniyal S, Onodera H, Wang D, St John N, et al. The mouse VLA-2 homologue supports collagen and laminin adhesion but not virus binding. Cell Adhes Commun. 1994;2:131-43 pubmed
  53. Carroll J, Romero M, Watt F. Suprabasal integrin expression in the epidermis of transgenic mice results in developmental defects and a phenotype resembling psoriasis. Cell. 1995;83:957-68 pubmed