RGD Reference Report - Structure-function analysis of the integrin beta 7 subunit: identification of domains involved in adhesion to MAdCAM-1. - Rat Genome Database

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Structure-function analysis of the integrin beta 7 subunit: identification of domains involved in adhesion to MAdCAM-1.

Authors: Tidswell, M  Pachynski, R  Wu, SW  Qiu, SQ  Dunham, E  Cochran, N  Briskin, MJ  Kilshaw, PJ  Lazarovits, AI  Andrew, DP  Butcher, EC  Yednock, TA  Erle, DJ 
Citation: Tidswell M, etal., J Immunol 1997 Aug 1;159(3):1497-505.
RGD ID: 633040
Pubmed: PMID:9233649   (View Abstract at PubMed)

Beta 7 integrins serve special roles in mucosal immunity. Alpha 4 beta 7-mediated adhesion to mucosal addressin cell adhesion molecule-1 (MAdCAM-1) directs lymphocyte homing to the gut, and alpha E beta 7 mediates binding of lymphocytes to E-cadherin on epithelial cells. Since alpha 4 beta 7 mediates adhesion to MAdCAM-1 but alpha 4 beta 1 does not, we used beta 7/beta 1 chimeras to directly assess the importance of specific regions of beta 7 in MAdCAM-1 binding. We found a region of beta 7 (residues 46-386) that accounts for specificity of alpha 4 beta 7 binding to MAdCAM-1. We also used human/mouse and human/rat chimeric beta 7 subunits to map epitopes recognized by fifteen anti-beta 7 mAbs. Six of seven Abs that block adhesion to MAdCAM-1 and E-cadherin (Fib 21, 22, 27, 30, 504; Act-1) mapped to amino acid residues 176-250. Residues 176-250 lie within the region of beta 7 that specifies MAdCAM-1 binding and also within a region that has a predicted structure homologous to the metal ion-dependent adhesion site (MIDAS) domains of the integrin subunits alpha L and alpha M. Three new Abs that recognize beta 7 in the presence of Mn2+, but not Ca2+, and promote adhesion to MAdCAM-1, mapped to amino acids 46-149. One blocking and five other Abs mapped to other regions (amino acids 387-725). We conclude that a MIDAS-like domain serves a critical role in beta 7 integrin-mediated adhesion.

Molecular Pathway Annotations    Click to see Annotation Detail View

RGD Manual Annotations

TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
integrin mediated signaling pathway   TAS 633040 RGD 
Objects Annotated

Genes (Rattus norvegicus)
Itgb7  (integrin subunit beta 7)


Additional Information