Integrin beta 4 explained

Integrin, beta 4 (ITGB4) also known as CD104 (Cluster of Differentiation 104), is a human gene.^[1]

Function

Integrins are heterodimers composed of alpha and beta subunits, that are noncovalently associated transmembrane glycoprotein receptors. Different combinations of alpha and beta polypeptides form complexes that vary in their ligand-binding specificities. Integrins mediate cell-matrix or cell-cell adhesion, and transduced signals that regulate gene expression and cell growth. This gene encodes the integrin beta 4 subunit, a receptor for the laminins. This subunit tends to associate with alpha 6 subunit and is likely to play a pivotal role in the biology of invasive carcinoma. Mutations in this gene are associated with epidermolysis bullosa with pyloric atresia. Multiple alternatively spliced transcript variants encoding distinct isoforms have been found for this gene.

Interactions

ITGB4 has been shown to interact with Collagen, type XVII, alpha 1,^{[2] [3]} EIF6^[4] and Erbin.^[5]

See also

• Cluster of differentiation
• List of target antigens in pemphigoid

References

Further reading

• Lipscomb EA, Mercurio AM . Mobilization and activation of a signaling competent alpha6beta4integrin underlies its contribution to carcinoma progression . Cancer and Metastasis Reviews . 24 . 3 . 413–23 . Sep 2005 . 16258729 . 10.1007/s10555-005-5133-4 . 26150860 .
• Sonnenberg A, Linders CJ, Modderman PW, Damsky CH, 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 . The Journal of Cell Biology . 110 . 6 . 2145–55 . Jun 1990 . 1693624 . 2116116 . 10.1083/jcb.110.6.2145 .
• Tamura RN, Rozzo C, Starr L, Chambers J, Reichardt LF, Cooper HM, Quaranta V . Epithelial integrin alpha 6 beta 4: complete primary structure of alpha 6 and variant forms of beta 4 . The Journal of Cell Biology . 111 . 4 . 1593–604 . Oct 1990 . 1976638 . 2116232 . 10.1083/jcb.111.4.1593 .
• Hogervorst F, Kuikman I, van Kessel AG, Sonnenberg A . Molecular cloning of the human alpha 6 integrin subunit. Alternative splicing of alpha 6 mRNA and chromosomal localization of the alpha 6 and beta 4 genes . European Journal of Biochemistry . 199 . 2 . 425–33 . Jul 1991 . 2070796 . 10.1111/j.1432-1033.1991.tb16140.x . free .
• Vogel BE, Tarone G, Giancotti FG, Gailit J, Ruoslahti E . A novel fibronectin receptor with an unexpected subunit composition (alpha v beta 1) . The Journal of Biological Chemistry . 265 . 11 . 5934–7 . Apr 1990 . 10.1016/S0021-9258(19)39268-3 . 2138612 . free .
• Suzuki S, Naitoh Y . Amino acid sequence of a novel integrin beta 4 subunit and primary expression of the mRNA in epithelial cells . The EMBO Journal . 9 . 3 . 757–63 . Mar 1990 . 2311577 . 551732 . 10.1002/j.1460-2075.1990.tb08170.x.
• Hogervorst F, Kuikman I, von dem Borne AE, Sonnenberg A . Cloning and sequence analysis of beta-4 cDNA: an integrin subunit that contains a unique 118 kd cytoplasmic domain . The EMBO Journal . 9 . 3 . 765–70 . Mar 1990 . 2311578 . 551734 . 10.1002/j.1460-2075.1990.tb08171.x.
• Kajiji S, Tamura RN, Quaranta V . A novel integrin (alpha E beta 4) from human epithelial cells suggests a fourth family of integrin adhesion receptors . The EMBO Journal . 8 . 3 . 673–80 . Mar 1989 . 2542022 . 400860 . 10.1002/j.1460-2075.1989.tb03425.x.
• Hemler ME, Crouse C, Sonnenberg A . Association of the VLA alpha 6 subunit with a novel protein. A possible alternative to the common VLA beta 1 subunit on certain cell lines . The Journal of Biological Chemistry . 264 . 11 . 6529–35 . Apr 1989 . 10.1016/S0021-9258(18)83380-4 . 2649503 . free .
• Vidal F, Aberdam D, Miquel C, Christiano AM, Pulkkinen L, Uitto J, Ortonne JP, Meneguzzi G . Integrin beta 4 mutations associated with junctional epidermolysis bullosa with pyloric atresia . Nature Genetics . 10 . 2 . 229–34 . Jun 1995 . 7545057 . 10.1038/ng0695-229 . 24894174 .
• Mainiero F, Pepe A, Wary KK, Spinardi L, Mohammadi M, Schlessinger J, Giancotti FG . Signal transduction by the alpha 6 beta 4 integrin: distinct beta 4 subunit sites mediate recruitment of Shc/Grb2 and association with the cytoskeleton of hemidesmosomes . The EMBO Journal . 14 . 18 . 4470–81 . Sep 1995 . 7556090 . 394539 . 10.1002/j.1460-2075.1995.tb00126.x.
• Clarke AS, Lotz MM, Mercurio AM . A novel structural variant of the human beta 4 integrin cDNA . Cell Adhesion and Communication . 2 . 1 . 1–6 . Apr 1994 . 7982032 . 10.3109/15419069409014197 .
• Weeks BS, Desai K, Loewenstein PM, Klotman ME, Klotman PE, Green M, Kleinman HK . Identification of a novel cell attachment domain in the HIV-1 Tat protein and its 90-kDa cell surface binding protein . The Journal of Biological Chemistry . 268 . 7 . 5279–84 . Mar 1993 . 10.1016/S0021-9258(18)53530-4 . 8444901 . free .
• Iacovacci S, Gagnoux-Palacios L, Zambruno G, Meneguzzi G, D'Alessio M . Genomic organization of the human integrin beta4 gene . Mammalian Genome . 8 . 6 . 448–50 . Jun 1997 . 9166594 . 10.1007/s003359900467 . 41037975 .
• Mainiero F, Murgia C, Wary KK, Curatola AM, Pepe A, Blumemberg M, Westwick JK, Der CJ, Giancotti FG . The coupling of alpha6beta4 integrin to Ras-MAP kinase pathways mediated by Shc controls keratinocyte proliferation . The EMBO Journal . 16 . 9 . 2365–75 . May 1997 . 9171350 . 1169837 . 10.1093/emboj/16.9.2365 .
• Pulkkinen L, Kurtz K, Xu Y, Bruckner-Tuderman L, Uitto J . Genomic organization of the integrin beta 4 gene (ITGB4): a homozygous splice-site mutation in a patient with junctional epidermolysis bullosa associated with pyloric atresia . Laboratory Investigation . 76 . 6 . 823–33 . Jun 1997 . 9194858 .
• van Leusden MR, Kuikman I, Sonnenberg A . The unique cytoplasmic domain of the human integrin variant beta4E is produced by partial retention of intronic sequences . Biochemical and Biophysical Research Communications . 235 . 3 . 826–30 . Jun 1997 . 9207246 . 10.1006/bbrc.1997.6892 .
• von Bredow DC, Nagle RB, Bowden GT, Cress AE . Cleavage of beta 4 integrin by matrilysin . Experimental Cell Research . 236 . 1 . 341–5 . Oct 1997 . 9344615 . 10.1006/excr.1997.3711 .
• Biffo S, Sanvito F, Costa S, Preve L, Pignatelli R, Spinardi L, Marchisio PC . Isolation of a novel beta4 integrin-binding protein (p27(BBP)) highly expressed in epithelial cells . The Journal of Biological Chemistry . 272 . 48 . 30314–21 . Nov 1997 . 9374518 . 10.1074/jbc.272.48.30314 . free .
• Pulkkinen L, Kim DU, Uitto J . Epidermolysis bullosa with pyloric atresia: novel mutations in the beta4 integrin gene (ITGB4) . The American Journal of Pathology . 152 . 1 . 157–66 . Jan 1998 . 9422533 . 1858138 .
• Hughes AE, Bradley DT, Campbell M, Lechner J, Dash DP, Simpson DA, Willoughby CE . Mutation altering the miR-184 seed region causes familial keratoconus with cataract . American Journal of Human Genetics . 89 . 5 . 628–33 . Nov 2011 . 21996275 . 3213395 . 10.1016/j.ajhg.2011.09.014 .

External links

• GeneReviews/NCBI/NIH/UW entry on Epidermolysis Bullosa with Pyloric Atresia
  • ITGB4 Info with links in the Cell Migration Gateway

Notes and References

1. Web site: Entrez Gene: ITGB4 integrin, beta 4.
2. Aho S, Uitto J . Direct interaction between the intracellular domains of bullous pemphigoid antigen 2 (BP180) and beta 4 integrin, hemidesmosomal components of basal keratinocytes . Biochemical and Biophysical Research Communications . 243 . 3 . 694–9 . Feb 1998 . 9500991 . 10.1006/bbrc.1998.8162 .
3. Schaapveld RQ, Borradori L, Geerts D, van Leusden MR, Kuikman I, Nievers MG, Niessen CM, Steenbergen RD, Snijders PJ, Sonnenberg A . Hemidesmosome formation is initiated by the beta4 integrin subunit, requires complex formation of beta4 and HD1/plectin, and involves a direct interaction between beta4 and the bullous pemphigoid antigen 180 . The Journal of Cell Biology . 142 . 1 . 271–84 . Jul 1998 . 9660880 . 2133016 . 10.1083/jcb.142.1.271 .
4. Biffo S, Sanvito F, Costa S, Preve L, Pignatelli R, Spinardi L, Marchisio PC . Isolation of a novel beta4 integrin-binding protein (p27(BBP)) highly expressed in epithelial cells . The Journal of Biological Chemistry . 272 . 48 . 30314–21 . Nov 1997 . 9374518 . 10.1074/jbc.272.48.30314 . free .
5. Favre B, Fontao L, Koster J, Shafaatian R, Jaunin F, Saurat JH, Sonnenberg A, Borradori L . The hemidesmosomal protein bullous pemphigoid antigen 1 and the integrin beta 4 subunit bind to ERBIN. Molecular cloning of multiple alternative splice variants of ERBIN and analysis of their tissue expression . The Journal of Biological Chemistry . 276 . 35 . 32427–36 . Aug 2001 . 11375975 . 10.1074/jbc.M011005200 . free .