JCB logo
Avanti Polar Lipids, Inc.
  Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents
Published online February 26, 2007
doi:10.1083/jcb.200608010
The Journal of Cell Biology, Vol. 176, No. 5, 667-680
The Rockefeller University Press, 0021-9525 $30.00
© 2007 Schober et al.
This Article
Right arrow Full Text
Right arrow Full Text (PDF, 5317K)
Right arrow PPT slides of all figures
Right arrow Supplemental Material Index
Right arrow Alert me when this article is cited
Right arrow Citation Map
Services
Right arrow Email this article
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new content in the JCB
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via CrossRef
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Schober, M.
Right arrow Articles by Fuchs, E.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Schober, M.
Right arrow Articles by Fuchs, E.
Social Bookmarking
Add to CiteULike   Add to Complore   Add to Connotea   Add to Del.icio.us   Add to Digg   Add to Reddit   Add to Technorati  
What's this?

Article

Focal adhesion kinase modulates tension signaling to control actin and focal adhesion dynamics



Markus Schober1, Srikala Raghavan1, Maria Nikolova1, Lisa Polak1, H. Amalia Pasolli1, Hilary E. Beggs2, Louis F. Reichardt2, and Elaine Fuchs1

1 Howard Hughes Medical Institute, Laboratory of Mammalian Cell Biology and Development, The Rockefeller University, New York, NY 10021
2 Department of Physiology, University of California, San Francisco, San Francisco, CA 94143

Correspondence to Elaine Fuchs: fuchs{at}rockefeller.edu

In response to {alpha}ß1 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 {alpha}ß1 integrins. FAK is also dispensible for proliferation/survival in enriched medium. In contrast, FAK functions downstream of {alpha}ß1 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.

S. Raghavan's present address is College of Dental Medicine and Department of Dermatology, Columbia University, New York, NY 10032.

Abbreviations used in this paper: cKO, conditional KO; FA, focal adhesion; FN, fibronectin; GAP, GTPase-activating protein; ILK, integrin-linked kinase; KO, knockout; MK, mouse keratinocyte; MLC, myosin light chain; MYPT, myosin phosphatase target; PAK, p21-activated kinase; PIX, PAK-interacting exchange factor; PKL, p95 paxillin kinase linker; PXN, paxillin; PYK2, proline-rich tyrosine kinase 2; ROCK, Rho kinase; VIN, vinculin; WT, wild-type.


Add to CiteULike CiteULike   Add to Complore Complore   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us   Add to Digg Digg   Add to Reddit Reddit   Add to Technorati Technorati    What's this?


This article has been cited by other articles:



  Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents