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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...

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Autores principales: Jones, Matthew C., Machida, Kazuya, Mayer, Bruce J., Turner, Christopher E.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The American Society for Cell Biology 2013
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.
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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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