Vascular cell adhesion protein 1 also known as vascular cell adhesion molecule 1 (VCAM-1) or cluster of differentiation 106 (CD106) is a protein that in humans is encoded by the VCAM1 gene. VCAM-1 functions as a [1 ] cell adhesion molecule.
Structure [ edit ]
The VCAM-1 gene contains six or seven
immunoglobulin domains, and is expressed on both large and small blood vessels only after the endothelial cells are stimulated by cytokines. It is alternatively spliced into two known RNA transcripts that encode different isoforms in humans. The gene product is a cell surface [2 ] sialoglycoprotein, a type I membrane protein that is a member of the Ig superfamily.
Function [ edit ]
The VCAM-1 protein mediates the adhesion of
lymphocytes, monocytes, eosinophils, and basophils to vascular endothelium. It also functions in leukocyte-endothelial cell signal transduction, and it may play a role in the development of atherosclerosis and rheumatoid arthritis.
Upregulation of VCAM-1 in endothelial cells by cytokines occurs as a result of increased
gene transcription (e.g., in response to Tumor necrosis factor-alpha (TNF-α) and Interleukin-1 (IL-1)) and through stabilization of Messenger RNA (mRNA) (e.g., Interleukin-4 (IL-4)). The promoter region of the VCAM-1 gene contains functional tandem NF-κB (nuclear factor-kappa B) sites. The sustained expression of VCAM-1 lasts over 24 hours.
Primarily, the VCAM-1 protein is an endothelial
ligand for VLA-4 (Very Late Antigen-4 or α4β1) of the β1 subfamily of integrins, and for integrin α4β7. VCAM-1 expression has also been observed in other cell types (e.g., smooth muscle cells). It has also been shown to interact with EZR and [3 ] Moesin. [3 ]
Pharmacology [ edit ]
melanoma cells can use VCAM-1 to adhere to the endothelium, and VCAM-1 may participate in monocyte recruitment to atherosclerotic sites. As a result, VCAM-1 is a potential [4 ] drug target.
References [ edit ]
^ Cybulsky M, Fries JW, Williams AJ, Sultan P, Eddy RL, Byers MG et al. (1991). "The human VCAM1 gene is assigned to chromosome 1p31-p32". Cytogenet. Cell Genet. 58: 1852. doi: 10.1159/000133735.
^ "Entrez Gene: VCAM1 vascular cell adhesion molecule 1".
^ a b Barreiro O, Yanez-Mo M, Serrador JM, Montoya MC, Vicente-Manzanares M, Tejedor R et al. (Jun 2002). "Dynamic interaction of VCAM-1 and ICAM-1 with moesin and ezrin in a novel endothelial docking structure for adherent leukocytes". J. Cell Biol. 157 (7): 1233–45. doi: 10.1083/jcb.200112126. PMC 2173557. PMID 12082081.
^ Eibl RH and Benoit M (2004). "Molecular resolution of cell adhesion forces.". IEE Proc Nanobiotechnol. 151 (3): 128-32. doi: 10.1049/ip-nbt:20040707. PMID 16475855.
Further reading [ edit ]
External links [ edit ]
1ij9: Highly Hydrated Human VCAM-1 Fragment
1vca: CRYSTAL STRUCTURE OF AN INTEGRIN-BINDING FRAGMENT OF VASCULAR CELL ADHESION MOLECULE-1 AT 1.8 ANGSTROMS RESOLUTION