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Paxillin phosphorylation at Ser273 localizes a GIT1–PIX–PAK complex and regulates adhesion and protrusion dynamics
Continuous adhesion formation and disassembly (adhesion turnover) in the protrusions of migrating cells is regulated by unclear mechanisms. We show that p21-activated kinase (PAK)–induced phosphorylation of serine 273 in paxillin is a critical regulator of this turnover. Paxillin-S273 phosphorylatio...
Autores principales: | , , , , , |
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Formato: | Texto |
Lenguaje: | English |
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The Rockefeller University Press
2006
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2063867/ https://www.ncbi.nlm.nih.gov/pubmed/16717130 http://dx.doi.org/10.1083/jcb.200509075 |
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author | Nayal, Anjana Webb, Donna J. Brown, Claire M. Schaefer, Erik M. Vicente-Manzanares, Miguel Horwitz, Alan Rick |
author_facet | Nayal, Anjana Webb, Donna J. Brown, Claire M. Schaefer, Erik M. Vicente-Manzanares, Miguel Horwitz, Alan Rick |
author_sort | Nayal, Anjana |
collection | PubMed |
description | Continuous adhesion formation and disassembly (adhesion turnover) in the protrusions of migrating cells is regulated by unclear mechanisms. We show that p21-activated kinase (PAK)–induced phosphorylation of serine 273 in paxillin is a critical regulator of this turnover. Paxillin-S273 phosphorylation dramatically increases migration, protrusion, and adhesion turnover by increasing paxillin–GIT1 binding and promoting the localization of a GIT1–PIX–PAK signaling module near the leading edge. Mutants that interfere with the formation of this ternary module abrogate the effects of paxillin-S273 phosphorylation. PAK-dependent paxillin-S273 phosphorylation functions in a positive-feedback loop, as active PAK, active Rac, and myosin II activity are all downstream effectors of this turnover pathway. Finally, our studies led us to identify in highly motile cells a class of small adhesions that reside near the leading edge, turnover in 20–30 s, and resemble those seen with paxillin-S273 phosphorylation. These adhesions appear to be regulated by the GIT1–PIX–PAK module near the leading edge. |
format | Text |
id | pubmed-2063867 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2006 |
publisher | The Rockefeller University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-20638672007-11-29 Paxillin phosphorylation at Ser273 localizes a GIT1–PIX–PAK complex and regulates adhesion and protrusion dynamics Nayal, Anjana Webb, Donna J. Brown, Claire M. Schaefer, Erik M. Vicente-Manzanares, Miguel Horwitz, Alan Rick J Cell Biol Research Articles Continuous adhesion formation and disassembly (adhesion turnover) in the protrusions of migrating cells is regulated by unclear mechanisms. We show that p21-activated kinase (PAK)–induced phosphorylation of serine 273 in paxillin is a critical regulator of this turnover. Paxillin-S273 phosphorylation dramatically increases migration, protrusion, and adhesion turnover by increasing paxillin–GIT1 binding and promoting the localization of a GIT1–PIX–PAK signaling module near the leading edge. Mutants that interfere with the formation of this ternary module abrogate the effects of paxillin-S273 phosphorylation. PAK-dependent paxillin-S273 phosphorylation functions in a positive-feedback loop, as active PAK, active Rac, and myosin II activity are all downstream effectors of this turnover pathway. Finally, our studies led us to identify in highly motile cells a class of small adhesions that reside near the leading edge, turnover in 20–30 s, and resemble those seen with paxillin-S273 phosphorylation. These adhesions appear to be regulated by the GIT1–PIX–PAK module near the leading edge. The Rockefeller University Press 2006-05-22 /pmc/articles/PMC2063867/ /pubmed/16717130 http://dx.doi.org/10.1083/jcb.200509075 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 Nayal, Anjana Webb, Donna J. Brown, Claire M. Schaefer, Erik M. Vicente-Manzanares, Miguel Horwitz, Alan Rick Paxillin phosphorylation at Ser273 localizes a GIT1–PIX–PAK complex and regulates adhesion and protrusion dynamics |
title | Paxillin phosphorylation at Ser273 localizes a GIT1–PIX–PAK complex and regulates adhesion and protrusion dynamics |
title_full | Paxillin phosphorylation at Ser273 localizes a GIT1–PIX–PAK complex and regulates adhesion and protrusion dynamics |
title_fullStr | Paxillin phosphorylation at Ser273 localizes a GIT1–PIX–PAK complex and regulates adhesion and protrusion dynamics |
title_full_unstemmed | Paxillin phosphorylation at Ser273 localizes a GIT1–PIX–PAK complex and regulates adhesion and protrusion dynamics |
title_short | Paxillin phosphorylation at Ser273 localizes a GIT1–PIX–PAK complex and regulates adhesion and protrusion dynamics |
title_sort | paxillin phosphorylation at ser273 localizes a git1–pix–pak complex and regulates adhesion and protrusion dynamics |
topic | Research Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2063867/ https://www.ncbi.nlm.nih.gov/pubmed/16717130 http://dx.doi.org/10.1083/jcb.200509075 |
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