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Genetic analysis of β1 integrin “activation motifs” in mice
Akey feature of integrins is their ability to regulate the affinity for ligands, a process termed integrin activation. The final step in integrin activation is talin binding to the NPXY motif of the integrin β cytoplasmic domains. Talin binding disrupts the salt bridge between the α/β tails, leading...
Autores principales: | , , , , |
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Formato: | Texto |
Lenguaje: | English |
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The Rockefeller University Press
2006
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2064342/ https://www.ncbi.nlm.nih.gov/pubmed/16954348 http://dx.doi.org/10.1083/jcb.200604060 |
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author | Czuchra, Aleksandra Meyer, Hannelore Legate, Kyle R. Brakebusch, Cord Fässler, Reinhard |
author_facet | Czuchra, Aleksandra Meyer, Hannelore Legate, Kyle R. Brakebusch, Cord Fässler, Reinhard |
author_sort | Czuchra, Aleksandra |
collection | PubMed |
description | Akey feature of integrins is their ability to regulate the affinity for ligands, a process termed integrin activation. The final step in integrin activation is talin binding to the NPXY motif of the integrin β cytoplasmic domains. Talin binding disrupts the salt bridge between the α/β tails, leading to tail separation and integrin activation. We analyzed mice in which we mutated the tyrosines of the β1 tail and the membrane-proximal aspartic acid required for the salt bridge. Tyrosine-to-alanine substitutions abolished β1 integrin functions and led to a β1 integrin–null phenotype in vivo. Surprisingly, neither the substitution of the tyrosines with phenylalanine nor the aspartic acid with alanine resulted in an obvious defect. These data suggest that the NPXY motifs of the β1 integrin tail are essential for β1 integrin function, whereas tyrosine phosphorylation and the membrane-proximal salt bridge between α and β1 tails have no apparent function under physiological conditions in vivo. |
format | Text |
id | pubmed-2064342 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2006 |
publisher | The Rockefeller University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-20643422007-11-29 Genetic analysis of β1 integrin “activation motifs” in mice Czuchra, Aleksandra Meyer, Hannelore Legate, Kyle R. Brakebusch, Cord Fässler, Reinhard J Cell Biol Research Articles Akey feature of integrins is their ability to regulate the affinity for ligands, a process termed integrin activation. The final step in integrin activation is talin binding to the NPXY motif of the integrin β cytoplasmic domains. Talin binding disrupts the salt bridge between the α/β tails, leading to tail separation and integrin activation. We analyzed mice in which we mutated the tyrosines of the β1 tail and the membrane-proximal aspartic acid required for the salt bridge. Tyrosine-to-alanine substitutions abolished β1 integrin functions and led to a β1 integrin–null phenotype in vivo. Surprisingly, neither the substitution of the tyrosines with phenylalanine nor the aspartic acid with alanine resulted in an obvious defect. These data suggest that the NPXY motifs of the β1 integrin tail are essential for β1 integrin function, whereas tyrosine phosphorylation and the membrane-proximal salt bridge between α and β1 tails have no apparent function under physiological conditions in vivo. The Rockefeller University Press 2006-09-11 /pmc/articles/PMC2064342/ /pubmed/16954348 http://dx.doi.org/10.1083/jcb.200604060 Text en Copyright © 2006, The Rockefeller University Press This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/4.0/). |
spellingShingle | Research Articles Czuchra, Aleksandra Meyer, Hannelore Legate, Kyle R. Brakebusch, Cord Fässler, Reinhard Genetic analysis of β1 integrin “activation motifs” in mice |
title | Genetic analysis of β1 integrin “activation motifs” in mice |
title_full | Genetic analysis of β1 integrin “activation motifs” in mice |
title_fullStr | Genetic analysis of β1 integrin “activation motifs” in mice |
title_full_unstemmed | Genetic analysis of β1 integrin “activation motifs” in mice |
title_short | Genetic analysis of β1 integrin “activation motifs” in mice |
title_sort | genetic analysis of β1 integrin “activation motifs” in mice |
topic | Research Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2064342/ https://www.ncbi.nlm.nih.gov/pubmed/16954348 http://dx.doi.org/10.1083/jcb.200604060 |
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