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The alpha(4) integrin subunit Tyr(187) has a key role in alpha(4)beta(7)-dependent cell adhesion

Authors :
Ruiz-Velasco, Natividad
Guerrero-Esteo, Mercedes
Briskin, Michel J.
Teixidó, Joaquín
Ministerio de Educación y Ciencia (España)
Teixidó, Joaquín
Teixidó, Joaquín [0000-0002-3177-4151]
Source :
Digital.CSIC. Repositorio Institucional del CSIC, instname
Publication Year :
2000
Publisher :
American Society for Biochemistry and Molecular Biology, 2000.

Abstract

9 p.-6 fig.-1 tab.<br />The integrin alpha(4)beta(7) is the cell adhesion receptor for the mucosal vascular addressin MAdCAM-1, and this interaction is dominant in lymphocyte homing to Peyer's patch high endothelial venules, and plays key roles in lymphocyte recruitment at sites of inflammation. To identify alpha(4) subunit amino acids important for alpha(4)beta(7)/MAd-CAM-1 interaction, we expressed mutant alpha(4) and wild type beta(7) chains in K562 cells and analyzed the effect of the mutations on cell adhesion to a soluble MAdCAM-1 (sMAdCAM-1-Ig), Transfectants expressing mutated alpha(4) at Tyr(187) displayed a substantial decrease in adhesion to this ligand, which was associated with a reduced alpha(4)beta(7)/sMAdCAM-1-Ig interaction, as determined by soluble binding assays. Addition of Mn2+ to the adhesion assays did not restore the impaired adhesion. Mutations at alpha(4) Gln(152)Asp(153) also affected transfectant adhesion to sMAdCAM-1-Ig, but did not involve an alteration of alpha(4)beta(7)/MAdCAM-1 binding, and adhesion was restored by Mn2+. Instead, mutations at alpha(4) Asn(123)Glu(124) did not affect this adhesion. Mutation of alpha(4) Tyr(187) abolished alpha(4)beta(7)-mediated cell adhesion to CS-1/fibronectin, an additional ligand for alpha(4)beta(7), while alpha(4) Gln(152)Asp(153) transfectant mutants showed a reduced adhesion, These results identify alpha(4), Tyr(187) as a key residue during receptor alpha(4)beta(7)/ligand interactions, indicating that it plays important roles in alpha(4)beta(7)-mediated leukocyte adhesion, and provide a potential target for therapeutic intervention in several inflammatory pathologies.<br />This work was supported by Grants PM95-0017 and SAF99-0057 from the plan General del Conocimiento-Ministerio de Educaciòn y Ciencia (Spain).

Details

Language :
English
Database :
OpenAIRE
Journal :
Digital.CSIC. Repositorio Institucional del CSIC, instname
Accession number :
edsair.dedup.wf.001..b6bcdce413265c9a1cdeba31ca2f863b