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Gene Review

Itgb5  -  integrin beta 5

Mus musculus

Synonyms: AA475909, AI874634, ESTM23, Integrin beta-5, beta-5, ...
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Disease relevance of Itgb5


High impact information on Itgb5


Chemical compound and disease context of Itgb5

  • Undifferentiated epithelia express high levels of alpha v beta 5 integrins and are easily infected with recombinant adenoviruses; gene transfer is completely inhibited with excess fiber and partially inhibited with RGD peptide and alpha v beta 5 integrin antibody [8].

Biological context of Itgb5

  • We have shown previously that oligodendrocyte precursors in vitro express a limited repertoire of integrins, including alpha 6 beta 1, alpha v beta 3, and that differentiation is associated with downregulation of alpha v beta 1 and upregulation of alpha v beta 5 [9].
  • In summary, we have identified a 19-bp cis-element mediating GM-CSF-induced down-regulation of beta5 by a mechanism requiring protein synthesis [10].
  • Expression of this construct in cultured human embryonic kidney cells under the control of the inducible metallothionein promoter resulted in cell rounding and detachment, and blocked cell adhesion mediated by the beta 1 and alpha v beta 5 integrins [11].
  • Using deletion mutants, we localized a 109-base pair (bp) promoter region responsible for GM-CSF-inhibited beta5 transcription [10].
  • A 13-kilobase (kb) genomic fragment containing part of the beta5 gene was isolated by screening a mouse genomic library with a probe derived from the most 5'-end of a murine beta5 cDNA [10].

Anatomical context of Itgb5

  • On the other hand, the beta3 integrin mRNA was found only in large and round cells (presumptive germ cells), whereas beta5 integrin was localized in gonadal somatic cells, with the exception of coelomic epithelial cells [12].
  • To examine the in vivo function of this receptor, we have generated mice lacking beta5 expression, using homologous recombination in embryonic stem cells [3].
  • Keratinocytes harvested from beta5(-/-) mice demonstrate impaired migration on and adhesion to the alphavbeta5 ligand, vitronectin [3].
  • We previously noted that the initial receptor by which murine osteoclast precursors bind matrix is the integrin alphav beta5 and that granulocyte-macrophage colony-stimulating factor (GM-CSF) decreases expression of this heterodimer by suppressing transcription of the beta5 gene [10].
  • The groove is large enough to accommodate the loop between beta-strands beta4 and beta5 of the lectin domain of E-selectin that has been implicated in neutrophil adhesion (1) [13].

Associations of Itgb5 with chemical compounds

  • Northern analysis demonstrates that cycloheximide treatment abrogates the capacity of GM-CSF to decrease beta5 mRNA levels [10].
  • Mice lacking the integrin beta5 subunit have accelerated osteoclast maturation and increased activity in the estrogen-deficient state [14].
  • A notable feature of the distribution of the beta 5 subunit in the glandular and luminal epithelium is its apical localization, which may suggest an involvement in implantation [15].
  • The induction of migration was blocked by alpha v beta 5-specific antibodies and required Arg-Gly-Asp sites in L1 [16].
  • Glra1 assembles into a pentameric complex with the beta subunit of the glycine receptor (3 alpha (1)2 beta 5) to form a glycine-gated chloride channel [17].

Regulatory relationships of Itgb5

  • Expression of alpha v beta 5 in tumor cells promoted their adhesion to vitronectin in vitro [2].
  • We propose that ectodomain-released L1 promotes migration by autocrine/paracrine stimulation via alpha v beta 5 [16].
  • In C57BL/6 mice, most M-MuLV-specific CD8+ CTL clones and immune PBL coexpressed V alpha3.2 in association with V beta5 [18].
  • The G protein beta5 expressed in transfected COS cells was properly folded as its pattern of stable C-terminal proteolytic fragments was identical to that of native brain beta5 [19].
  • RGS/beta5 complexes may contribute to the selectivity of signal transduction initiated by receptors coupled to G(i) and G(o) by binding to phospholipase C and stimulating the GTPase activity of Galpha(o) [20].

Other interactions of Itgb5

  • The expressions of integrin beta3, beta5, and beta6 were unaltered [21].
  • Analysis of adhesive functions of transfected cells shows that beta1B interferes in a dominant negative manner with beta1A and beta3/beta5 integrins in cell spreading, focal adhesion formation, focal adhesion kinase tyrosine phosphorylation, and fibronectin matrix assembly [22].
  • This subunit is known to associate with beta 5, and we therefore suggest that integrin alpha v beta 5 is involved in epithelial-mesenchymal interactions during tooth development [23].
  • The RET phosphopeptide binds to Dok1 via a surface groove formed between strand beta5 and the C-terminal alpha-helix of the PTB domain [24].
  • Transforming growth factor-beta up-regulates the beta 5 integrin subunit expression via Sp1 and Smad signaling [25].

Analytical, diagnostic and therapeutic context of Itgb5


  1. Enhanced pathological angiogenesis in mice lacking beta3 integrin or beta3 and beta5 integrins. Reynolds, L.E., Wyder, L., Lively, J.C., Taverna, D., Robinson, S.D., Huang, X., Sheppard, D., Hynes, R.O., Hodivala-Dilke, K.M. Nat. Med. (2002) [Pubmed]
  2. Insulin-like growth factor receptor cooperates with integrin alpha v beta 5 to promote tumor cell dissemination in vivo. Brooks, P.C., Klemke, R.L., Schon, S., Lewis, J.M., Schwartz, M.A., Cheresh, D.A. J. Clin. Invest. (1997) [Pubmed]
  3. Normal development, wound healing, and adenovirus susceptibility in beta5-deficient mice. Huang, X., Griffiths, M., Wu, J., Farese, R.V., Sheppard, D. Mol. Cell. Biol. (2000) [Pubmed]
  4. A direct test of potential roles for beta3 and beta5 integrins in growth and metastasis of murine mammary carcinomas. Taverna, D., Crowley, D., Connolly, M., Bronson, R.T., Hynes, R.O. Cancer Res. (2005) [Pubmed]
  5. Mouse egg integrin alpha 6 beta 1 functions as a sperm receptor. Almeida, E.A., Huovila, A.P., Sutherland, A.E., Stephens, L.E., Calarco, P.G., Shaw, L.M., Mercurio, A.M., Sonnenberg, A., Primakoff, P., Myles, D.G., White, J.M. Cell (1995) [Pubmed]
  6. T-cell tolerance by clonal anergy in transgenic mice with nonlymphoid expression of MHC class II I-E. Burkly, L.C., Lo, D., Kanagawa, O., Brinster, R.L., Flavell, R.A. Nature (1989) [Pubmed]
  7. Loss of synchronized retinal phagocytosis and age-related blindness in mice lacking alphavbeta5 integrin. Nandrot, E.F., Kim, Y., Brodie, S.E., Huang, X., Sheppard, D., Finnemann, S.C. J. Exp. Med. (2004) [Pubmed]
  8. Expression of alpha v beta 5 integrin is necessary for efficient adenovirus-mediated gene transfer in the human airway. Goldman, M.J., Wilson, J.M. J. Virol. (1995) [Pubmed]
  9. A role in migration for the alpha V beta 1 integrin expressed on oligodendrocyte precursors. Milner, R., Edwards, G., Streuli, C., Ffrench-Constant, C. J. Neurosci. (1996) [Pubmed]
  10. Cloning of the murine beta5 integrin subunit promoter. Identification of a novel sequence mediating granulocyte-macrophage colony-stimulating factor-dependent repression of beta5 integrin gene transcription. Feng, X., Teitelbaum, S.L., Quiroz, M.E., Towler, D.A., Ross, F.P. J. Biol. Chem. (1999) [Pubmed]
  11. Disruption of integrin function and induction of tyrosine phosphorylation by the autonomously expressed beta 1 integrin cytoplasmic domain. Lukashev, M.E., Sheppard, D., Pytela, R. J. Biol. Chem. (1994) [Pubmed]
  12. Expression pattern of alphavbeta3 and alphavbeta5 integrin mRNA in mouse fetal gonads. Ishii, M., Tay, T.W., Matsui, T., Kidokoro, T., Mizukami, T., Kanai, Y., Hayashi, Y., Kurohmaru, M. J. Reprod. Dev. (2006) [Pubmed]
  13. Primary and tertiary structures of the Fab fragment of a monoclonal anti-E-selectin 7A9 antibody that inhibits neutrophil attachment to endothelial cells. Rodríguez-Romero, A., Almog, O., Tordova, M., Randhawa, Z., Gilliland, G.L. J. Biol. Chem. (1998) [Pubmed]
  14. Mice lacking the integrin beta5 subunit have accelerated osteoclast maturation and increased activity in the estrogen-deficient state. Lane, N.E., Yao, W., Nakamura, M.C., Humphrey, M.B., Kimmel, D., Huang, X., Sheppard, D., Ross, F.P., Teitelbaum, S.L. J. Bone Miner. Res. (2005) [Pubmed]
  15. Integrins beta 5, beta 3 and alpha v are apically distributed in endometrial epithelium. Aplin, J.D., Spanswick, C., Behzad, F., Kimber, S.J., Vićovac, L. Mol. Hum. Reprod. (1996) [Pubmed]
  16. Ectodomain shedding of L1 adhesion molecule promotes cell migration by autocrine binding to integrins. Mechtersheimer, S., Gutwein, P., Agmon-Levin, N., Stoeck, A., Oleszewski, M., Riedle, S., Postina, R., Fahrenholz, F., Fogel, M., Lemmon, V., Altevogt, P. J. Cell Biol. (2001) [Pubmed]
  17. A frameshift mutation in the mouse alpha 1 glycine receptor gene (Glra1) results in progressive neurological symptoms and juvenile death. Buckwalter, M.S., Cook, S.A., Davisson, M.T., White, W.F., Camper, S.A. Hum. Mol. Genet. (1994) [Pubmed]
  18. Flow-microfluorometric monitoring of oligoclonal CD8+ T cell responses to an immunodominant Moloney leukemia virus-encoded epitope in vivo. Brawand, P., Biasi, G., Horvath, C., Cerottini, J.C., MacDonald, H.R. J. Immunol. (1998) [Pubmed]
  19. Selective activation of effector pathways by brain-specific G protein beta5. Zhang, S., Coso, O.A., Lee, C., Gutkind, J.S., Simonds, W.F. J. Biol. Chem. (1996) [Pubmed]
  20. Regulators of G protein signaling 6 and 7. Purification of complexes with gbeta5 and assessment of their effects on g protein-mediated signaling pathways. Posner, B.A., Gilman, A.G., Harris, B.A. J. Biol. Chem. (1999) [Pubmed]
  21. Cloning of mouse integrin alphaV cDNA and role of the alphaV-related matrix receptors in metanephric development. Wada, J., Kumar, A., Liu, Z., Ruoslahti, E., Reichardt, L., Marvaldi, J., Kanwar, Y.S. J. Cell Biol. (1996) [Pubmed]
  22. beta1-integrin cytoplasmic subdomains involved in dominant negative function. Retta, S.F., Balzac, F., Ferraris, P., Belkin, A.M., Fässler, R., Humphries, M.J., De Leo, G., Silengo, L., Tarone, G. Mol. Biol. Cell (1998) [Pubmed]
  23. Integrin subunit expression associated with epithelial-mesenchymal interactions during murine tooth development. Salmivirta, K., Gullberg, D., Hirsch, E., Altruda, F., Ekblom, P. Dev. Dyn. (1996) [Pubmed]
  24. Structural basis for the specific recognition of RET by the Dok1 phosphotyrosine binding domain. Shi, N., Ye, S., Bartlam, M., Yang, M., Wu, J., Liu, Y., Sun, F., Han, X., Peng, X., Qiang, B., Yuan, J., Rao, Z. J. Biol. Chem. (2004) [Pubmed]
  25. Transforming growth factor-beta up-regulates the beta 5 integrin subunit expression via Sp1 and Smad signaling. Lai, C.F., Feng, X., Nishimura, R., Teitelbaum, S.L., Avioli, L.V., Ross, F.P., Cheng, S.L. J. Biol. Chem. (2000) [Pubmed]
  26. Integrin regulatory switching in development: oscillation of beta 5 integrin mRNA expression during epithelial-mesenchymal interactions in tooth development. Yamada, S., Yamada, K.M., Brown, K.E. Int. J. Dev. Biol. (1994) [Pubmed]
  27. Prominent beta-5 gene expression in the cardiovascular system and in the cartilaginous primordiae of the skeleton during mouse development. Le Gat, L., Bonnel, S., Gogat, K., Brizard, M., Van Den Berghe, L., Kobetz, A., Gadin, S., Dureau, P., Dufier, J.L., Abitbol, M., Menasche, M. Cell Commun. Adhes. (2001) [Pubmed]
  28. RIII S/J (H-2r). An inbred mouse strain with a massive deletion of T cell receptor V beta genes. Haqqi, T.M., Banerjee, S., Anderson, G.D., David, C.S. J. Exp. Med. (1989) [Pubmed]
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