Source:http://linkedlifedata.com/resource/pubmed/id/16585601
Switch to
| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
8
|
| pubmed:dateCreated |
2006-4-4
|
| pubmed:abstractText |
Cell adhesion mediated by the interaction between integrin alpha4beta1 and VCAM-1 is important in normal physiologic processes and in inflammatory and autoimmune disease. Numerous studies have mapped the alpha4beta1 binding sites in VCAM-1 that mediate cell adhesion; however, little is known about the regions in VCAM-1 important for regulating soluble binding. In the present study, we demonstrate that 6D VCAM-1 (an alternatively spliced isoform of VCAM-1 lacking Ig-like domain 4) binds alpha4beta1 with a higher relative affinity than does the full-length form of VCAM-1 containing 7 Ig-like extracellular domains (7D VCAM-1). In indirect binding assays, the EC50 of soluble 6D VCAM-1 binding to alpha4beta1 on Jurkat cells (in 1 mM MnCl2) was 2 x 10(-9) M, compared with 7D VCAM-1 at 11 x 10(-9) M. When used in solution to inhibit alpha4beta1 mediated cell adhesion, the IC50 of 6D VCAM-1 was 13 x 10(-9) M, compared with 7D VCAM-1 measured at 150 x 10(-9) M. Removal of Ig-like domains 4, 5, or 6, or simply substituting Asp328 in domain 4 of 7D VCAM-1 with alanine, caused increased binding of soluble 7D VCAM-1 to alpha4beta1. In contrast, cells adhered more avidly to 7D VCAM-1 under shear force, as it induced cell spreading at lower concentrations than did 6D VCAM-1. Finally, soluble 6D VCAM-1 acts as an agonist through alpha4beta1 by augmenting cell migration and inducing cell aggregation. These results indicate that the domain 4 of VCAM-1 plays a contrasting role when VCAM-1 is presented in solution or as a cell surface-expressed adhesive substrate.
|
| pubmed:grant | |
| pubmed:language |
eng
|
| pubmed:journal | |
| pubmed:citationSubset |
AIM
|
| pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/DNA,
http://linkedlifedata.com/resource/pubmed/chemical/Integrin alpha4beta1,
http://linkedlifedata.com/resource/pubmed/chemical/Intercellular Adhesion Molecule-1,
http://linkedlifedata.com/resource/pubmed/chemical/Recombinant Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Vascular Cell Adhesion Molecule-1
|
| pubmed:status |
MEDLINE
|
| pubmed:month |
Apr
|
| pubmed:issn |
0022-1767
|
| pubmed:author | |
| pubmed:issnType |
Print
|
| pubmed:day |
15
|
| pubmed:volume |
176
|
| pubmed:owner |
NLM
|
| pubmed:authorsComplete |
Y
|
| pubmed:pagination |
5041-9
|
| pubmed:dateRevised |
2007-11-14
|
| pubmed:meshHeading |
pubmed-meshheading:16585601-Alternative Splicing,
pubmed-meshheading:16585601-Amino Acid Sequence,
pubmed-meshheading:16585601-Base Sequence,
pubmed-meshheading:16585601-Binding Sites,
pubmed-meshheading:16585601-Cell Adhesion,
pubmed-meshheading:16585601-Cell Aggregation,
pubmed-meshheading:16585601-Cell Line,
pubmed-meshheading:16585601-Cell Movement,
pubmed-meshheading:16585601-DNA,
pubmed-meshheading:16585601-Humans,
pubmed-meshheading:16585601-Integrin alpha4beta1,
pubmed-meshheading:16585601-Intercellular Adhesion Molecule-1,
pubmed-meshheading:16585601-Jurkat Cells,
pubmed-meshheading:16585601-Kinetics,
pubmed-meshheading:16585601-Mutagenesis,
pubmed-meshheading:16585601-Protein Structure, Tertiary,
pubmed-meshheading:16585601-Recombinant Proteins,
pubmed-meshheading:16585601-Solubility,
pubmed-meshheading:16585601-Vascular Cell Adhesion Molecule-1
|
| pubmed:year |
2006
|
| pubmed:articleTitle |
Contrasting roles for domain 4 of VCAM-1 in the regulation of cell adhesion and soluble VCAM-1 binding to integrin alpha4beta1.
|
| pubmed:affiliation |
Encysive Pharmaceuticals Incorporated, Houston, TX 77030, USA. dwoodside@encysive.com
|
| pubmed:publicationType |
Journal Article,
In Vitro,
Research Support, U.S. Gov't, Non-P.H.S.,
Research Support, Non-U.S. Gov't,
Research Support, N.I.H., Extramural
|