Integrin alpha 4 explained

CD49d is an integrin alpha subunit. It makes up half of the α4β1 lymphocyte homing receptor.

Function

The product of this gene belongs to the integrin alpha chain family of proteins. Integrins are heterodimeric integral membrane proteins composed of an alpha chain and a beta chain. This gene encodes an alpha 4 chain. Unlike other integrin alpha chains, alpha 4 neither contains an I-domain, nor undergoes disulfide-linked cleavage. Alpha 4 chain associates with either beta 1 chain or beta 7 chain.^[1]

Interactions

CD49d has been shown to interact with LGALS8^[2] and Paxillin.^{[3] [4]}

See also

• Carotegrast methyl, an integrin alpha 4 antagonist used for the treatment of ulcerative colitis

Further reading

• Book: Humphries MJ, Sheridan J, Mould AP, Newham P . Mechanisms of VCAM-1 and Fibronectin Binding to Integrin α ₄ β ₁ : Implications for Integrin Function and Rational Drug Design . Ciba Foundation Symposium 189 - Cell Adhesion and Human Disease . Ciba Foundation Symposium . Novartis Foundation Symposia . 189 . 177–91; discussion 191–9 . 1995 . 7587632 . 10.1002/9780470514719.ch13. 978-0-470-51471-9 .
• Oostendorp RA, Dörmer P . VLA-4-mediated interactions between normal human hematopoietic progenitors and stromal cells. . Leuk. Lymphoma . 24 . 5–6 . 423–35 . 1997 . 9086434 . 10.3109/10428199709055581 .
• Porter JC, Hogg N . Integrins take partners: cross-talk between integrins and other membrane receptors. . Trends Cell Biol. . 8 . 10 . 390–6 . 1999 . 9789327 . 10.1016/S0962-8924(98)01344-0 .
• Rose DM, Han J, Ginsberg MH . Alpha4 integrins and the immune response. . Immunol. Rev. . 186 . 1 . 118–24 . 2003 . 12234367 . 10.1034/j.1600-065X.2002.18611.x . 37850994 .
• O'Connor P . Natalizumab and the role of alpha 4-integrin antagonism in the treatment of multiple sclerosis. . Expert Opinion on Biological Therapy . 7 . 1 . 123–36 . 2007 . 17150024 . 10.1517/14712598.7.1.123 . 73319319 .
• Chan BM, Elices MJ, Murphy E, Hemler ME . Adhesion to vascular cell adhesion molecule 1 and fibronectin. Comparison of alpha 4 beta 1 (VLA-4) and alpha 4 beta 7 on the human B cell line JY. . J. Biol. Chem. . 267 . 12 . 8366–70 . 1992 . 10.1016/S0021-9258(18)42453-2 . 1373725 . free .
• Fernández-Ruiz E, Pardo-Manuel de Villena F, Rubio MA, Corbí AL, Rodriguez de Córdoba S, Sánchez-Madrid F . Mapping of the human VLA-alpha 4 gene to chromosome 2q31-q32. . Eur. J. Immunol. . 22 . 2 . 587–90 . 1992 . 1537388 . 10.1002/eji.1830220243 . 86449765 .
• Rubio M, Nueda A, Vara A, Corbí Lopez AL . A single mRNA encodes the alpha 150 and alpha 80/70 forms of the alpha subunit of VLA4. . Eur. J. Immunol. . 22 . 4 . 1099–102 . 1992 . 1551405 . 10.1002/eji.1830220434 . 83613615 .
• 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. . J. Cell Biol. . 110 . 6 . 2145–55 . 1990 . 1693624 . 2116116 . 10.1083/jcb.110.6.2145 .
• Teixidó J, Parker CM, Kassner PD, Hemler ME . Functional and structural analysis of VLA-4 integrin alpha 4 subunit cleavage. . J. Biol. Chem. . 267 . 3 . 1786–91 . 1992 . 10.1016/S0021-9258(18)46014-0 . 1730718 . free .
• Rosemblatt M, Vuillet-Gaugler MH, Leroy C, Coulombel L . Coexpression of two fibronectin receptors, VLA-4 and VLA-5, by immature human erythroblastic precursor cells. . J. Clin. Invest. . 87 . 1 . 6–11 . 1991 . 1824634 . 294977 . 10.1172/JCI115002 .
• Rosen GD, Birkenmeier TM, Dean DC . Characterization of the alpha 4 integrin gene promoter. . Proc. Natl. Acad. Sci. U.S.A. . 88 . 10 . 4094–8 . 1991 . 2034655 . 51604 . 10.1073/pnas.88.10.4094 . 1991PNAS...88.4094R . free .
• Takada Y, Elices MJ, Crouse C, Hemler ME . The primary structure of the alpha 4 subunit of VLA-4: homology to other integrins and a possible cell-cell adhesion function. . EMBO J. . 8 . 5 . 1361–8 . 1989 . 2788572 . 400962 . 10.1002/j.1460-2075.1989.tb03516.x.
• Takada Y, Strominger JL, Hemler ME . The very late antigen family of heterodimers is part of a superfamily of molecules involved in adhesion and embryogenesis. . Proc. Natl. Acad. Sci. U.S.A. . 84 . 10 . 3239–43 . 1987 . 3033641 . 304844 . 10.1073/pnas.84.10.3239 . 1987PNAS...84.3239T . free .
• Hemler ME, Huang C, Schwarz L . The VLA protein family. Characterization of five distinct cell surface heterodimers each with a common 130,000 molecular weight beta subunit. . J. Biol. Chem. . 262 . 7 . 3300–9 . 1987 . 10.1016/S0021-9258(18)61504-2 . 3546305 . free .
• Gailit J, Pierschbacher M, Clark RA . Expression of functional alpha 4 beta 1 integrin by human dermal fibroblasts. . J. Invest. Dermatol. . 100 . 3 . 323–8 . 1993 . 8440915 . 10.1111/1523-1747.ep12470011 .
• Pujades C, Teixidó J, Bazzoni G, Hemler ME . Integrin alpha 4 cysteines 278 and 717 modulate VLA-4 ligand binding and also contribute to alpha 4/180 formation. . Biochem. J. . (Pt 3) . 3. 899–908 . 1996 . 8611173 . 1216996 . 10.1042/bj3130899. 313 .
• Szabo M, McIntyre BW . Identification of two variants of the human integrin alpha 4 subunit. . Mol. Immunol. . 32 . 17–18 . 1453–4 . 1996 . 8643114 . 10.1016/0161-5890(96)00001-6 .
• Mannion BA, Berditchevski F, Kraeft SK, Chen LB, Hemler ME . Transmembrane-4 superfamily proteins CD81 (TAPA-1), CD82, CD63, and CD53 specifically associated with integrin alpha 4 beta 1 (CD49d/CD29). . J. Immunol. . 157 . 5 . 2039–47 . 1996 . 10.4049/jimmunol.157.5.2039 . 8757325 . 1977096 . free .

External links

• • ITGA4 Info with links in the Cell Migration Gateway

Notes and References

1. Web site: Entrez Gene: ITGA4 integrin, alpha 4 (antigen CD49D, alpha 4 subunit of VLA-4 receptor).
2. Hadari YR, Arbel-Goren R, Levy Y, Amsterdam A, Alon R, Zakut R, Zick Y . Galectin-8 binding to integrins inhibits cell adhesion and induces apoptosis . J. Cell Sci. . 113 . Pt 13 . 2385–97 . 2000 . 10.1242/jcs.113.13.2385 . 10852818 .
3. Han J, Liu S, Rose DM, Schlaepfer DD, McDonald H, Ginsberg MH . Phosphorylation of the integrin alpha 4 cytoplasmic domain regulates paxillin binding . J. Biol. Chem. . 276 . 44 . 40903–9 . November 2001 . 11533025 . 10.1074/jbc.M102665200 . free .
4. Liu S, Kiosses WB, Rose DM, Slepak M, Salgia R, Griffin JD, Turner CE, Schwartz MA, Ginsberg MH . A fragment of paxillin binds the alpha 4 integrin cytoplasmic domain (tail) and selectively inhibits alpha 4-mediated cell migration . J. Biol. Chem. . 277 . 23 . 20887–94 . June 2002 . 11919182 . 10.1074/jbc.M110928200 . free .