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rdf:type |
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lifeskim:mentions |
umls-concept:C0001511,
umls-concept:C0020792,
umls-concept:C0021701,
umls-concept:C0330390,
umls-concept:C0936012,
umls-concept:C1314939,
umls-concept:C1514562,
umls-concept:C1711351,
umls-concept:C1880389,
umls-concept:C1883204,
umls-concept:C1883221
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pubmed:issue |
3
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pubmed:dateCreated |
1997-8-14
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pubmed:databankReference |
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pubmed:abstractText |
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.
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pubmed:grant |
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
AIM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Antibodies, Monoclonal,
http://linkedlifedata.com/resource/pubmed/chemical/Cations,
http://linkedlifedata.com/resource/pubmed/chemical/Cell Adhesion Molecules,
http://linkedlifedata.com/resource/pubmed/chemical/Immunoglobulins,
http://linkedlifedata.com/resource/pubmed/chemical/Integrin beta Chains,
http://linkedlifedata.com/resource/pubmed/chemical/Integrins,
http://linkedlifedata.com/resource/pubmed/chemical/Ligands,
http://linkedlifedata.com/resource/pubmed/chemical/MADCAM1 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Madcam1 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Madcam1 protein, rat,
http://linkedlifedata.com/resource/pubmed/chemical/Mucoproteins,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Lymphocyte Homing,
http://linkedlifedata.com/resource/pubmed/chemical/Recombinant Fusion Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Serine,
http://linkedlifedata.com/resource/pubmed/chemical/integrin beta7
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pubmed:status |
MEDLINE
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pubmed:month |
Aug
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pubmed:issn |
0022-1767
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pubmed:author |
pubmed-author:AndrewD PDP,
pubmed-author:BrissieE OEO,
pubmed-author:ButcherE CEC,
pubmed-author:CochranNN,
pubmed-author:DunhamEE,
pubmed-author:ErleD JDJ,
pubmed-author:KilshawP JPJ,
pubmed-author:LazarovitsA IAI,
pubmed-author:NayR MRM,
pubmed-author:PachynskiRR,
pubmed-author:SuS CSC,
pubmed-author:TidswellMM,
pubmed-author:YednockT ATA
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pubmed:issnType |
Print
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pubmed:day |
1
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pubmed:volume |
159
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
1497-505
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pubmed:dateRevised |
2007-11-14
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pubmed:meshHeading |
pubmed-meshheading:9233649-Animals,
pubmed-meshheading:9233649-Antibodies, Monoclonal,
pubmed-meshheading:9233649-Cations,
pubmed-meshheading:9233649-Cell Adhesion Molecules,
pubmed-meshheading:9233649-Epitope Mapping,
pubmed-meshheading:9233649-Humans,
pubmed-meshheading:9233649-Immunoglobulins,
pubmed-meshheading:9233649-Integrin beta Chains,
pubmed-meshheading:9233649-Integrins,
pubmed-meshheading:9233649-Leukemia, Erythroblastic, Acute,
pubmed-meshheading:9233649-Ligands,
pubmed-meshheading:9233649-Mice,
pubmed-meshheading:9233649-Molecular Sequence Data,
pubmed-meshheading:9233649-Mucoproteins,
pubmed-meshheading:9233649-Protein Binding,
pubmed-meshheading:9233649-Protein Structure, Tertiary,
pubmed-meshheading:9233649-Rats,
pubmed-meshheading:9233649-Receptors, Lymphocyte Homing,
pubmed-meshheading:9233649-Recombinant Fusion Proteins,
pubmed-meshheading:9233649-Serine,
pubmed-meshheading:9233649-Structure-Activity Relationship,
pubmed-meshheading:9233649-Transfection,
pubmed-meshheading:9233649-Tumor Cells, Cultured
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pubmed:year |
1997
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pubmed:articleTitle |
Structure-function analysis of the integrin beta 7 subunit: identification of domains involved in adhesion to MAdCAM-1.
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pubmed:affiliation |
Lung Biology Center, Department of Medicine, University of California, San Francisco 94143, USA. easd@itsa.ucsf.edu
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.,
Research Support, Non-U.S. Gov't
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