A role for the protein tyrosine phosphatase CD45 in macrophage adhesion through the regulation of paxillin degradation.
CD45 is a protein tyrosine phosphatase expressed on all cells of hematopoietic origin that is known to regulate Src family kinases. In macrophages, the absence of CD45 has been linked to defects in adhesion, however the molecular mechanisms involved remain poorly defined. In this study, we show that...
| Main Authors: | , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2013-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC3729947?pdf=render |
| _version_ | 1818487071128420352 |
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| author | Joëlle St-Pierre Hanne L Ostergaard |
| author_facet | Joëlle St-Pierre Hanne L Ostergaard |
| author_sort | Joëlle St-Pierre |
| collection | DOAJ |
| description | CD45 is a protein tyrosine phosphatase expressed on all cells of hematopoietic origin that is known to regulate Src family kinases. In macrophages, the absence of CD45 has been linked to defects in adhesion, however the molecular mechanisms involved remain poorly defined. In this study, we show that bone marrow derived macrophages from CD45-deficient mice exhibit abnormal cell morphology and defective motility. These defects are accompanied by substantially decreased levels of the cytoskeletal-associated protein paxillin, without affecting the levels of other proteins. Degradation of paxillin in CD45-deficient macrophages is calpain-mediated, as treatment with a calpain inhibitor restores paxillin levels in these cells and enhances cell spreading. Inhibition of the tyrosine kinases proline-rich tyrosine kinase (Pyk2) and focal adhesion kinase (FAK), kinases that are capable of mediating tyrosine phosphorylation of paxillin, also restored paxillin levels, indicating a role for these kinases in the CD45-dependent regulation of paxillin. These data demonstrate that CD45 functions to regulate Pyk2/FAK activity, likely through the activity of Src family kinases, which in turn regulates the levels of paxillin to modulate macrophage adhesion and migration. |
| first_indexed | 2024-12-10T16:32:27Z |
| format | Article |
| id | doaj.art-fbc784ffd5ca4a4da664f35c9fd53c60 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-10T16:32:27Z |
| publishDate | 2013-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-fbc784ffd5ca4a4da664f35c9fd53c602022-12-22T01:41:31ZengPublic Library of Science (PLoS)PLoS ONE1932-62032013-01-0187e7153110.1371/journal.pone.0071531A role for the protein tyrosine phosphatase CD45 in macrophage adhesion through the regulation of paxillin degradation.Joëlle St-PierreHanne L OstergaardCD45 is a protein tyrosine phosphatase expressed on all cells of hematopoietic origin that is known to regulate Src family kinases. In macrophages, the absence of CD45 has been linked to defects in adhesion, however the molecular mechanisms involved remain poorly defined. In this study, we show that bone marrow derived macrophages from CD45-deficient mice exhibit abnormal cell morphology and defective motility. These defects are accompanied by substantially decreased levels of the cytoskeletal-associated protein paxillin, without affecting the levels of other proteins. Degradation of paxillin in CD45-deficient macrophages is calpain-mediated, as treatment with a calpain inhibitor restores paxillin levels in these cells and enhances cell spreading. Inhibition of the tyrosine kinases proline-rich tyrosine kinase (Pyk2) and focal adhesion kinase (FAK), kinases that are capable of mediating tyrosine phosphorylation of paxillin, also restored paxillin levels, indicating a role for these kinases in the CD45-dependent regulation of paxillin. These data demonstrate that CD45 functions to regulate Pyk2/FAK activity, likely through the activity of Src family kinases, which in turn regulates the levels of paxillin to modulate macrophage adhesion and migration.http://europepmc.org/articles/PMC3729947?pdf=render |
| spellingShingle | Joëlle St-Pierre Hanne L Ostergaard A role for the protein tyrosine phosphatase CD45 in macrophage adhesion through the regulation of paxillin degradation. PLoS ONE |
| title | A role for the protein tyrosine phosphatase CD45 in macrophage adhesion through the regulation of paxillin degradation. |
| title_full | A role for the protein tyrosine phosphatase CD45 in macrophage adhesion through the regulation of paxillin degradation. |
| title_fullStr | A role for the protein tyrosine phosphatase CD45 in macrophage adhesion through the regulation of paxillin degradation. |
| title_full_unstemmed | A role for the protein tyrosine phosphatase CD45 in macrophage adhesion through the regulation of paxillin degradation. |
| title_short | A role for the protein tyrosine phosphatase CD45 in macrophage adhesion through the regulation of paxillin degradation. |
| title_sort | role for the protein tyrosine phosphatase cd45 in macrophage adhesion through the regulation of paxillin degradation |
| url | http://europepmc.org/articles/PMC3729947?pdf=render |
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