Am J Physiol Cell Physiol AJP: Endocrinology and Metabolism
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     

Am J Physiol Cell Physiol 292: C1339-C1352, 2007. First published November 29, 2006; doi:10.1152/ajpcell.00144.2006
0363-6143/07 $8.00
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
292/4/C1339    most recent
00144.2006v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Web of Science (10)
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Huang, D.
Right arrow Articles by Bryer-Ash, M.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Huang, D.
Right arrow Articles by Bryer-Ash, M.

GROWTH, DIFFERENTIATION, AND APOPTOSIS

Focal adhesion kinase mediates cell survival via NF-{kappa}B and ERK signaling pathways

Danshan Huang,1,2 Michelle Khoe,2 Merone Befekadu,2 Sue Chung,2 Yasunori Takata,2 Dusko Ilic,3 and Michael Bryer-Ash1,2

1West Los Angeles Veterans Administration Medical Center, the 2Gonda (Goldschmied) Diabetes Center, Division of Endocrinology, Diabetes and Hypertension, David Geffen School of Medicine at UCLA, Los Angeles, California; and 3Department of Stomatology and Anatomy, University of California, San Francisco, California

Submitted 30 March 2006 ; accepted in final form 26 November 2006

Focal adhesion kinase (FAK) is important to cellular functions such as proliferation, migration, and survival of anchorage-dependent cells. We investigated the role of FAK in modulating normal cellular responses, specifically cell survival in response to inflammatory stimuli and serum withdrawal, using FAK-knockout (FAK–/–) embryonic fibroblasts. FAK–/– fibroblasts were more vulnerable to TNF-{alpha}-induced apoptosis, as measured by terminal deoxynucleotidyl transferase positivity. FAK–/– fibroblasts also demonstrated increased procaspase-3 cleavage to p17 subunit, whereas this was undetectable in FAK+/+ fibroblasts. Insulin receptor substrate-1 expression was completely abolished and NF-{kappa}B activity was reduced, with a concomitant decrease in abundance of the anti-apoptotic protein Bcl-xL in FAK–/– cells. Upon serum withdrawal, FAK+/+ cells exhibited marked attenuation of basal ERK phosphorylation, while FAK–/– cells, in contrast, maintained high basal ERK phosphorylation. Moreover, inhibition of ERK phosphorylation potentiated serum withdrawal-induced caspase-3 activity. This was paralleled by increased insulin receptor substrate (IRS)-2 expression in FAK–/– cells, although both insulin- and IGF-1-mediated phosphorylation of Akt/PKB and GSK-3 were impaired. This suggests that IRS-2 protects against apoptosis upon serum withdrawal via the ERK signaling pathway. The specific role of FAK to protect cells from apoptosis is regulated by activation and phosphorylation of NF-{kappa}B and interaction between activated growth factor anti-apoptotic signaling pathways involving both phosphatidylinositol 3-kinase/Akt and MAPK/ERK1/2. We demonstrate that FAK is necessary for upregulation of the anti-apoptotic NF-{kappa}B response, as well as for normal expression of growth factor signaling proteins. Thus we propose a novel role for FAK in protection from cytokine-mediated apoptosis.

apoptosis; ERK1/2; insulin; TNF-{alpha}; IGF-1


Address for reprint requests and other correspondence: M. Bryer-Ash, UCLA Division of Endocrinology, Diabetes and Hypertension, 900 Veteran Ave., Warren Hall, Rm. 24-130, Los Angeles, CA 90095 (e-mail: mbryerash{at}mednet.ucla.edu)




This article has been cited by other articles:


Home page
 Infect. Immun.Home page
A. E. Lin, K. Krastel, R. I. Hobb, S. A. Thompson, D. G. Cvitkovitch, and E. C. Gaynor
Atypical Roles for Campylobacter jejuni Amino Acid ATP Binding Cassette Transporter Components PaqP and PaqQ in Bacterial Stress Tolerance and Pathogen-Host Cell Dynamics
Infect. Immun., November 1, 2009; 77(11): 4912 - 4924.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Cell Physiol.Home page
S. Chien, J.-J. Chiu, and Y.-S. Li
Focal adhesion kinase phosphorylation in flow-activation of endothelial NF-{kappa}B. Focus on "Focal adhesion kinase modulates activation of NF-{kappa}B by flow in endothelial cells"
Am J Physiol Cell Physiol, October 1, 2009; 297(4): C800 - C801.
[Full Text] [PDF]

Home page
 Am. J. Physiol. Renal Physiol.Home page
K. J. Kelly, P. Wu, C. E. Patterson, C. Temm, and J. H. Dominguez
LOX-1 and inflammation: a new mechanism for renal injury in obesity and diabetes
Am J Physiol Renal Physiol, May 1, 2008; 294(5): F1136 - F1145.
[Abstract] [Full Text] [PDF]

Home page
 BloodHome page
A. M. Roccaro, X. Leleu, A. Sacco, X. Jia, M. Melhem, A.-S. Moreau, H. T. Ngo, J. Runnels, A. Azab, F. Azab, et al.
Dual targeting of the proteasome regulates survival and homing in Waldenstrom macroglobulinemia
Blood, May 1, 2008; 111(9): 4752 - 4763.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Visit Other APS Journals Online
Copyright © 2007 by the American Physiological Society.