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Focal adhesion kinase modulates tension signaling to control actin and focal adhesion dynamics
In response to αβ1 integrin signaling, transducers such as focal adhesion kinase (FAK) become activated, relaying to specific machineries and triggering distinct cellular responses. By conditionally ablating Fak in skin epidermis and culturing Fak-null keratinocytes, we show that FAK is dispensable...
Autores principales: | , , , , , , , |
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Formato: | Texto |
Lenguaje: | English |
Publicado: |
The Rockefeller University Press
2007
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2064024/ https://www.ncbi.nlm.nih.gov/pubmed/17325207 http://dx.doi.org/10.1083/jcb.200608010 |
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author | Schober, Markus Raghavan, Srikala Nikolova, Maria Polak, Lisa Pasolli, H. Amalia Beggs, Hilary E. Reichardt, Louis F. Fuchs, Elaine |
author_facet | Schober, Markus Raghavan, Srikala Nikolova, Maria Polak, Lisa Pasolli, H. Amalia Beggs, Hilary E. Reichardt, Louis F. Fuchs, Elaine |
author_sort | Schober, Markus |
collection | PubMed |
description | In response to αβ1 integrin signaling, transducers such as focal adhesion kinase (FAK) become activated, relaying to specific machineries and triggering distinct cellular responses. By conditionally ablating Fak in skin epidermis and culturing Fak-null keratinocytes, we show that FAK is dispensable for epidermal adhesion and basement membrane assembly, both of which require αβ1 integrins. FAK is also dispensible for proliferation/survival in enriched medium. In contrast, FAK functions downstream of αβ1 integrin in regulating cytoskeletal dynamics and orchestrating polarized keratinocyte migration out of epidermal explants. Fak-null keratinocytes display an aberrant actin cytoskeleton, which is tightly associated with robust, peripheral focal adhesions and microtubules. We find that without FAK, Src, p190RhoGAP, and PKL–PIX–PAK, localization and/or activation at focal adhesions are impaired, leading to elevated Rho activity, phosphorylation of myosin light chain kinase, and enhanced tensile stress fibers. We show that, together, these FAK-dependent activities are critical to control the turnover of focal adhesions, which is perturbed in the absence of FAK. |
format | Text |
id | pubmed-2064024 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2007 |
publisher | The Rockefeller University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-20640242007-11-29 Focal adhesion kinase modulates tension signaling to control actin and focal adhesion dynamics Schober, Markus Raghavan, Srikala Nikolova, Maria Polak, Lisa Pasolli, H. Amalia Beggs, Hilary E. Reichardt, Louis F. Fuchs, Elaine J Cell Biol Research Articles In response to αβ1 integrin signaling, transducers such as focal adhesion kinase (FAK) become activated, relaying to specific machineries and triggering distinct cellular responses. By conditionally ablating Fak in skin epidermis and culturing Fak-null keratinocytes, we show that FAK is dispensable for epidermal adhesion and basement membrane assembly, both of which require αβ1 integrins. FAK is also dispensible for proliferation/survival in enriched medium. In contrast, FAK functions downstream of αβ1 integrin in regulating cytoskeletal dynamics and orchestrating polarized keratinocyte migration out of epidermal explants. Fak-null keratinocytes display an aberrant actin cytoskeleton, which is tightly associated with robust, peripheral focal adhesions and microtubules. We find that without FAK, Src, p190RhoGAP, and PKL–PIX–PAK, localization and/or activation at focal adhesions are impaired, leading to elevated Rho activity, phosphorylation of myosin light chain kinase, and enhanced tensile stress fibers. We show that, together, these FAK-dependent activities are critical to control the turnover of focal adhesions, which is perturbed in the absence of FAK. The Rockefeller University Press 2007-02-26 /pmc/articles/PMC2064024/ /pubmed/17325207 http://dx.doi.org/10.1083/jcb.200608010 Text en Copyright © 2007, 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 Schober, Markus Raghavan, Srikala Nikolova, Maria Polak, Lisa Pasolli, H. Amalia Beggs, Hilary E. Reichardt, Louis F. Fuchs, Elaine Focal adhesion kinase modulates tension signaling to control actin and focal adhesion dynamics |
title | Focal adhesion kinase modulates tension signaling to control actin and focal adhesion dynamics |
title_full | Focal adhesion kinase modulates tension signaling to control actin and focal adhesion dynamics |
title_fullStr | Focal adhesion kinase modulates tension signaling to control actin and focal adhesion dynamics |
title_full_unstemmed | Focal adhesion kinase modulates tension signaling to control actin and focal adhesion dynamics |
title_short | Focal adhesion kinase modulates tension signaling to control actin and focal adhesion dynamics |
title_sort | focal adhesion kinase modulates tension signaling to control actin and focal adhesion dynamics |
topic | Research Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2064024/ https://www.ncbi.nlm.nih.gov/pubmed/17325207 http://dx.doi.org/10.1083/jcb.200608010 |
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