VLA-4 ( Eng. Very Late Antigen-4 ; integrin α 4 β 1 ) is a membrane protein , heterodimeric integrin receptor of the β1 integrin subfamily ( VLA receptors), consisting of the α4 alpha chain (CD49d) and β1 beta chain (CD29 ) It plays a role in the adhesion of leukocytes at the site of inflammation . The ligand of this receptor is a cell adhesion molecule VCAM-1 expressed by activated endothelial cells.
| Integrin alpha-4 | |
|---|---|
| Designations | |
| Characters | ITGA4 ; Cd49d |
| Entrez gene | 3676 |
| Hgnc | 6140 |
| Omim | 192975 |
| Refseq | NM_000885 |
| Uniprot | P13612 |
| Other data | |
| Locus | 2nd hr. , 2q31 -q32 |
| Integrin Beta-1 | |
|---|---|
 ITGB1 molecule structure | |
| Designations | |
| Characters | ; FNRB, MSK12, MDF2, CD29 |
| Entrez gene | 3688 |
| Hgnc | 6153 |
| Omim | 135630 |
| Refseq | NM_002211 |
| Uniprot | P05556 |
| Other data | |
| Locus | 10th hr , 10p11.2 |
Content
- 1 Functions
- 2 In medicine
- 3 notes
- 4 Bibliography
- 5 Links
Functions
VLA-4 (CD49d / CD29) is a leukocyte receptor of VCAM-1 . Expressed on the surface of most leukocytes, on neutrophils appears only under special conditions, binds to VCAM-1 and fibronectin . In an inactive state, it binds to VCAM-1 on the surface of endothelial cells with low affinity. After leukocyte activation by chemokines , usually secreted by endothelial cells in the lesion, integrin changes conformation and binds VCAM-1 with high affinity, which leads to the adhesion of leukocytes to the damaged endothelium. VLA-4, alpha-4 / beta-7, LFA-1 and Mac-1 are the main integrins responsible for the adhesion of lymphocytes and myeloid cells at the site of inflammation. [one]
VLA-4 plays an important role in the homeostasis of the distribution of hematopoietic stem cells and mature lymphocytes in the body. [2]
In medicine
Inhibition of the interaction of VLA-4 with its ligand can promote the release and mobilization of stem cells in the blood. [3]
Notes
- ↑ Rose DM, Alon R., Ginsberg MH Integrin modulation and signaling in leukocyte adhesion and migration (Eng.) // Immunol. Rev. : journal. - 2007 .-- August ( vol. 218 ). - P. 126-134 . - DOI : 10.1111 / j.1600-065X.2007.00536.x . - PMID 17624949 .
- ↑ Imai Y., Shimaoka M., Kurokawa M. Essential roles of VLA-4 in the hematopoietic system (Eng.) // Int. J. Hematol. : journal. - 2010 .-- May ( vol. 91 , no. 4 ). - P. 569-575 . - DOI : 10.1007 / s12185-010-0555-3 . - PMID 20352381 .
- ↑ Rettig MP, Ansstas G., DiPersio JF Mobilization of hematopoietic stem and progenitor cells using inhibitors of CXCR4 and VLA-4 (Eng.) // Leukemia: journal. - 2012 .-- January ( vol. 26 , no. 1 ). - P. 34-53 . - DOI : 10.1038 / leu.2011.197 . - PMID 21886173 .
Bibliography
- Hyduk SJ, Cybulsky MI Role of alpha4beta1 integrins in chemokine-induced monocyte arrest under conditions of shear stress // Microcirculation: journal. - 2009 .-- January ( vol. 16 , no. 1 ). - P. 17-30 . - DOI : 10.1080 / 10739680802425195 . - PMID 18979279 .
- Brittain JE, Parise LV The alpha4beta1 integrin in sickle cell disease (neopr.) // Transfus Clin Biol. - 2008. - T. 15 , No. 1-2 . - S. 19-22 . - DOI : 10.1016 / j.tracli.2008.03.013 . - PMID 18501656 .
- Luster AD, Alon R., von Andrian UH Immune cell migration in inflammation: present and future therapeutic targets (Eng.) // Nat. Immunol. : journal. - 2005 .-- December ( vol. 6 , no. 12 ). - P. 1182-1190 . - DOI : 10.1038 / ni1275 . - PMID 16369557 .
Links
- ITGA4 ITGB1 Complex on the Cell Migration Gateway website
- VLA-4 (alpha4beta1) (Russian)