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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...

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Autores principales: Nayal, Anjana, Webb, Donna J., Brown, Claire M., Schaefer, Erik M., Vicente-Manzanares, Miguel, Horwitz, Alan Rick
Formato: Texto
Lenguaje:English
Publicado: The Rockefeller University Press 2006
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.
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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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