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Paxillin kinase linker (PKL) regulates Vav2 signaling during cell spreading and migration
The Rho family of GTPases plays an important role in coordinating dynamic changes in the cell migration machinery after integrin engagement with the extracellular matrix. Rho GTPases are activated by guanine nucleotide exchange factors (GEFs) and negatively regulated by GTPase-activating proteins (G...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
The American Society for Cell Biology
2013
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3681694/ https://www.ncbi.nlm.nih.gov/pubmed/23615439 http://dx.doi.org/10.1091/mbc.E12-09-0654 |
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author | Jones, Matthew C. Machida, Kazuya Mayer, Bruce J. Turner, Christopher E. |
author_facet | Jones, Matthew C. Machida, Kazuya Mayer, Bruce J. Turner, Christopher E. |
author_sort | Jones, Matthew C. |
collection | PubMed |
description | The Rho family of GTPases plays an important role in coordinating dynamic changes in the cell migration machinery after integrin engagement with the extracellular matrix. Rho GTPases are activated by guanine nucleotide exchange factors (GEFs) and negatively regulated by GTPase-activating proteins (GAPs). However, the mechanisms by which GEFs and GAPs are spatially and temporally regulated are poorly understood. Here the activity of the proto-oncogene Vav2, a GEF for Rac1, RhoA, and Cdc42, is shown to be regulated by a phosphorylation-dependent interaction with the ArfGAP PKL (GIT2). PKL is required for Vav2 activation downstream of integrin engagement and epidermal growth factor (EGF) stimulation. In turn, Vav2 regulates the subsequent redistribution of PKL and the Rac1 GEF β-PIX to focal adhesions after EGF stimulation, suggesting a feedforward signaling loop that coordinates PKL-dependent Vav2 activation and PKL localization. Of interest, Vav2 is required for the efficient localization of PKL and β-PIX to the leading edge of migrating cells, and knockdown of Vav2 results in a decrease in directional persistence and polarization in migrating cells, suggesting a coordination between PKL/Vav2 signaling and PKL/β-PIX signaling during cell migration. |
format | Online Article Text |
id | pubmed-3681694 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2013 |
publisher | The American Society for Cell Biology |
record_format | MEDLINE/PubMed |
spelling | pubmed-36816942013-08-30 Paxillin kinase linker (PKL) regulates Vav2 signaling during cell spreading and migration Jones, Matthew C. Machida, Kazuya Mayer, Bruce J. Turner, Christopher E. Mol Biol Cell Articles The Rho family of GTPases plays an important role in coordinating dynamic changes in the cell migration machinery after integrin engagement with the extracellular matrix. Rho GTPases are activated by guanine nucleotide exchange factors (GEFs) and negatively regulated by GTPase-activating proteins (GAPs). However, the mechanisms by which GEFs and GAPs are spatially and temporally regulated are poorly understood. Here the activity of the proto-oncogene Vav2, a GEF for Rac1, RhoA, and Cdc42, is shown to be regulated by a phosphorylation-dependent interaction with the ArfGAP PKL (GIT2). PKL is required for Vav2 activation downstream of integrin engagement and epidermal growth factor (EGF) stimulation. In turn, Vav2 regulates the subsequent redistribution of PKL and the Rac1 GEF β-PIX to focal adhesions after EGF stimulation, suggesting a feedforward signaling loop that coordinates PKL-dependent Vav2 activation and PKL localization. Of interest, Vav2 is required for the efficient localization of PKL and β-PIX to the leading edge of migrating cells, and knockdown of Vav2 results in a decrease in directional persistence and polarization in migrating cells, suggesting a coordination between PKL/Vav2 signaling and PKL/β-PIX signaling during cell migration. The American Society for Cell Biology 2013-06-15 /pmc/articles/PMC3681694/ /pubmed/23615439 http://dx.doi.org/10.1091/mbc.E12-09-0654 Text en © 2013 Jones et al. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0). “ASCB®,” “The American Society for Cell Biology®,” and “Molecular Biology of the Cell®” are registered trademarks of The American Society of Cell Biology. |
spellingShingle | Articles Jones, Matthew C. Machida, Kazuya Mayer, Bruce J. Turner, Christopher E. Paxillin kinase linker (PKL) regulates Vav2 signaling during cell spreading and migration |
title | Paxillin kinase linker (PKL) regulates Vav2 signaling during cell spreading and migration |
title_full | Paxillin kinase linker (PKL) regulates Vav2 signaling during cell spreading and migration |
title_fullStr | Paxillin kinase linker (PKL) regulates Vav2 signaling during cell spreading and migration |
title_full_unstemmed | Paxillin kinase linker (PKL) regulates Vav2 signaling during cell spreading and migration |
title_short | Paxillin kinase linker (PKL) regulates Vav2 signaling during cell spreading and migration |
title_sort | paxillin kinase linker (pkl) regulates vav2 signaling during cell spreading and migration |
topic | Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3681694/ https://www.ncbi.nlm.nih.gov/pubmed/23615439 http://dx.doi.org/10.1091/mbc.E12-09-0654 |
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