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Regulation of lamellipodial persistence, adhesion turnover, and motility in macrophages by focal adhesion kinase
Macrophages are a key component of the innate immune system. In this study, we investigate how focal adhesion kinase (FAK) and the related kinase Pyk2 integrate adhesion signaling and growth factor receptor signaling to regulate diverse macrophage functions. Primary bone marrow macrophages isolated...
Autores principales: | , , , , , , , , , |
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Formato: | Texto |
Lenguaje: | English |
Publicado: |
The Rockefeller University Press
2007
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2140030/ https://www.ncbi.nlm.nih.gov/pubmed/18070912 http://dx.doi.org/10.1083/jcb.200708093 |
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author | Owen, Katherine A. Pixley, Fiona J. Thomas, Keena S. Vicente-Manzanares, Miguel Ray, Brianne J. Horwitz, Alan F. Parsons, J. Thomas Beggs, Hilary E. Stanley, E. Richard Bouton, Amy H. |
author_facet | Owen, Katherine A. Pixley, Fiona J. Thomas, Keena S. Vicente-Manzanares, Miguel Ray, Brianne J. Horwitz, Alan F. Parsons, J. Thomas Beggs, Hilary E. Stanley, E. Richard Bouton, Amy H. |
author_sort | Owen, Katherine A. |
collection | PubMed |
description | Macrophages are a key component of the innate immune system. In this study, we investigate how focal adhesion kinase (FAK) and the related kinase Pyk2 integrate adhesion signaling and growth factor receptor signaling to regulate diverse macrophage functions. Primary bone marrow macrophages isolated from mice in which FAK is conditionally deleted from cells of the myeloid lineage exhibited elevated protrusive activity, altered adhesion dynamics, impaired chemotaxis, elevated basal Rac1 activity, and a marked inability to form stable lamellipodia necessary for directional locomotion. The contribution of FAK to macrophage function in vitro was substantiated in vivo by the finding that recruitment of monocytes to sites of inflammation was impaired in the absence of FAK. Decreased Pyk2 expression in primary macrophages also resulted in a diminution of invasive capacity. However, the combined loss of FAK and Pyk2 had no greater effect than the loss of either molecule alone, indicating that both kinases function within the same pathway to promote invasion. |
format | Text |
id | pubmed-2140030 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2007 |
publisher | The Rockefeller University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-21400302008-06-17 Regulation of lamellipodial persistence, adhesion turnover, and motility in macrophages by focal adhesion kinase Owen, Katherine A. Pixley, Fiona J. Thomas, Keena S. Vicente-Manzanares, Miguel Ray, Brianne J. Horwitz, Alan F. Parsons, J. Thomas Beggs, Hilary E. Stanley, E. Richard Bouton, Amy H. J Cell Biol Research Articles Macrophages are a key component of the innate immune system. In this study, we investigate how focal adhesion kinase (FAK) and the related kinase Pyk2 integrate adhesion signaling and growth factor receptor signaling to regulate diverse macrophage functions. Primary bone marrow macrophages isolated from mice in which FAK is conditionally deleted from cells of the myeloid lineage exhibited elevated protrusive activity, altered adhesion dynamics, impaired chemotaxis, elevated basal Rac1 activity, and a marked inability to form stable lamellipodia necessary for directional locomotion. The contribution of FAK to macrophage function in vitro was substantiated in vivo by the finding that recruitment of monocytes to sites of inflammation was impaired in the absence of FAK. Decreased Pyk2 expression in primary macrophages also resulted in a diminution of invasive capacity. However, the combined loss of FAK and Pyk2 had no greater effect than the loss of either molecule alone, indicating that both kinases function within the same pathway to promote invasion. The Rockefeller University Press 2007-12-17 /pmc/articles/PMC2140030/ /pubmed/18070912 http://dx.doi.org/10.1083/jcb.200708093 Text en Copyright © 2007, 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 Owen, Katherine A. Pixley, Fiona J. Thomas, Keena S. Vicente-Manzanares, Miguel Ray, Brianne J. Horwitz, Alan F. Parsons, J. Thomas Beggs, Hilary E. Stanley, E. Richard Bouton, Amy H. Regulation of lamellipodial persistence, adhesion turnover, and motility in macrophages by focal adhesion kinase |
title | Regulation of lamellipodial persistence, adhesion turnover, and motility in macrophages by focal adhesion kinase |
title_full | Regulation of lamellipodial persistence, adhesion turnover, and motility in macrophages by focal adhesion kinase |
title_fullStr | Regulation of lamellipodial persistence, adhesion turnover, and motility in macrophages by focal adhesion kinase |
title_full_unstemmed | Regulation of lamellipodial persistence, adhesion turnover, and motility in macrophages by focal adhesion kinase |
title_short | Regulation of lamellipodial persistence, adhesion turnover, and motility in macrophages by focal adhesion kinase |
title_sort | regulation of lamellipodial persistence, adhesion turnover, and motility in macrophages by focal adhesion kinase |
topic | Research Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2140030/ https://www.ncbi.nlm.nih.gov/pubmed/18070912 http://dx.doi.org/10.1083/jcb.200708093 |
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