Linked Life Data

9506980

Source:http://linkedlifedata.com/resource/pubmed/id/9506980

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
12
pubmed:dateCreated
1998-4-16
pubmed:abstractText
The amino acid motif LDV is the principal binding site for alpha4 integrins in fibronectin, and homologous motifs are recognized in vascular cell adhesion molecule-1 and MAdCAM-1. Three conserved LDV motifs (LDV-1 to 3) occur in the ectodomain of the human and mouse alpha4-subunit, the functions of which are unknown. We demonstrate here that alpha4-transfected fibroblasts with mutation in LDV-1 (D489N) behaved like alpha4-wild type but that LDV-2 (D698N) and LDV-3 (D811N) mutants were impaired in binding and spreading on alpha4-specific substrates. On the RGD-containing fibronectin fragment FN-120 there was an inverse behavior; now the alpha4-wild type and the LDV-1 mutant could not adhere whereas the two other mutants could. The beta1 chain was critical for the differential integrin response. Biochemical analysis demonstrated that the LDV-2 and -3 mutations reduced the strength of the alpha4beta1 association, favored the formation of alpha5beta1, and prevented the expression of alpha4beta7 on the cell surface. Our results indicate that LDV-2 and LDV-3 are critical for the formation of a functional heterodimer. The presence of similar amino acid motifs in ligands and the alpha4-subunit suggest that metal coordination plays an important role in integrin-ligand binding as well as for heterodimer formation.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Mar
pubmed:issn
0021-9258
pubmed:author
pubmed:issnType
Print
pubmed:day
20
pubmed:volume
273
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
6786-95
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed:year
1998
pubmed:articleTitle
Asp-698 and Asp-811 of the integrin alpha4-subunit are critical for the formation of a functional heterodimer.
pubmed:affiliation
Tumor Immunology Programme, 0710, German Cancer Research Center, D-69120 Heidelberg, Federal Republic of Germany.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't