HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

J. Biol. Chem., Vol. 278, Issue 31, 29359-29365, August 1, 2003

This Article Full Text Full Text (PDF) All Versions of this Article: 278/31/29359    most recent M213115200v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Funakoshi-Tago, M. Articles by Kasahara, T. Search for Related Content PubMed PubMed Citation Articles by Funakoshi-Tago, M. Articles by Kasahara, T. Social Bookmarking                      What's this?

Tumor Necrosis Factor-induced Nuclear Factor B Activation Is Impaired in Focal Adhesion Kinase-deficient Fibroblasts^*

Megumi Funakoshi-Tago , Yoshiko Sonoda , Saeko Tanaka , Kenichiro Hashimoto , Kenji Tago , Shin-ichi Tominaga  and Tadashi Kasahara  ¶

From the Department of Biochemistry, Kyoritsu College of Pharmacy, 1-5-30 Shibakoen, Minato-ku, Tokyo 105-8512, Japan and Department of Biochemistry, Jichi Medical School, 3311-1 Minamikawachi-machi, Tochigi-ken 329-0433, Japan

Focal adhesion kinase (FAK) is widely involved in important cellular functions such as proliferation, migration, and survival, although its roles in immune and inflammatory responses have yet to be explored. We demonstrate a critical role for FAK in the tumor necrosis factor (TNF)-induced activation of nuclear factor (NF)-B, using FAK-deficient (FAK–/–) embryonic fibroblasts. Interestingly, TNF-induced interleukin (IL)-6 production was nearly abolished in FAK–/– fibroblasts, whereas a normal level of production was obtained in FAK+/– or FAK+/+ fibroblasts. FAK deficiency did not affect the three types of mitogen-activated protein kinases, ERK, JNK, and p38. Similarly, TNF-induced activation of activator protein 1 or NF-IL-6 was not impaired in FAK–/– cells. Of note, TNF-induced NF-B DNA binding activity and activation of IB kinases (IKKs) were markedly impaired in FAK–/– cells, whereas the expression of TNF receptor I or other signaling molecules such as receptor-interacting protein (RIP), tumor necrosis factor receptor-associated factor 2 (TRAF2), IKK, IKK, and IKK was unchanged. Also, TNF-induced association of FAK with RIP and subsequent association of RIP with TRAF2 were not observed, resulting in a failure of RIP to recruit the IKK complex in FAK–/– cells. The reintroduction of wild type FAK into FAK–/– cells restored the interaction of RIP with TRAF2 and the IKK complex and allowed recovery of NF-B activation and subsequent IL-6 production. Thus, we propose a novel role for FAK in the NF-B activation pathway leading to the production of cytokines.

Received for publication, December 23, 2002 , and in revised form, May 12, 2003.

^* This study was supported by a grant-in-aid from the Ministry of Education, Culture, Science and Sports of Japan. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

^¶ To whom correspondence should be addressed. Tel./Fax: 81-3-5400-2697; E-mail: Kasahara-td{at}kyoritsu-ph.ac.jp.

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

This article has been cited by other articles:

				D. D. Schlaepfer, S. Hou, S.-T. Lim, A. Tomar, H. Yu, Y. Lim, D. A. Hanson, S. A. Uryu, J. Molina, and S. K. Mitra Tumor Necrosis Factor-{alpha} Stimulates Focal Adhesion Kinase Activity Required for Mitogen-activated Kinase-associated Interleukin 6 Expression J. Biol. Chem., June 15, 2007; 282(24): 17450 - 17459. [Abstract] [Full Text] [PDF]

				D. Huang, M. Khoe, M. Befekadu, S. Chung, Y. Takata, D. Ilic, and M. Bryer-Ash Focal adhesion kinase mediates cell survival via NF-{kappa}B and ERK signaling pathways Am J Physiol Cell Physiol, April 1, 2007; 292(4): C1339 - C1352. [Abstract] [Full Text] [PDF]

				K. S. Ahn, G. Sethi, and B. B. Aggarwal Embelin, an Inhibitor of X Chromosome-Linked Inhibitor-of-Apoptosis Protein, Blocks Nuclear Factor-{kappa}B (NF-{kappa}B) Signaling Pathway Leading to Suppression of NF-{kappa}B-Regulated Antiapoptotic and Metastatic Gene Products Mol. Pharmacol., January 1, 2007; 71(1): 209 - 219. [Abstract] [Full Text] [PDF]

				J. W. Triplett and F. M. Pavalko Disruption of {alpha}-actinin-integrin interactions at focal adhesions renders osteoblasts susceptible to apoptosis Am J Physiol Cell Physiol, November 1, 2006; 291(5): C909 - C921. [Abstract] [Full Text] [PDF]

				H. M. Zhang, K. M. Keledjian, J. N. Rao, T. Zou, L. Liu, B. S. Marasa, S. R. Wang, L. Ru, E. D. Strauch, and J.-Y. Wang Induced focal adhesion kinase expression suppresses apoptosis by activating NF-{kappa}B signaling in intestinal epithelial cells Am J Physiol Cell Physiol, May 1, 2006; 290(5): C1310 - C1320. [Abstract] [Full Text] [PDF]

				S. F. Liu and A. B. Malik NF-{kappa}B activation as a pathological mechanism of septic shock and inflammation Am J Physiol Lung Cell Mol Physiol, April 1, 2006; 290(4): L622 - L645. [Abstract] [Full Text] [PDF]

				A. G. Eliopoulos, S. Das, and P. N. Tsichlis The Tyrosine Kinase Syk Regulates TPL2 Activation Signals J. Biol. Chem., January 20, 2006; 281(3): 1371 - 1380. [Abstract] [Full Text] [PDF]

				X. Li and A. Minden PAK4 Functions in Tumor Necrosis Factor (TNF) {alpha}-induced Survival Pathways by Facilitating TRADD Binding to the TNF Receptor J. Biol. Chem., December 16, 2005; 280(50): 41192 - 41200. [Abstract] [Full Text] [PDF]

				C. Urbinati, A. Bugatti, M. Giacca, D. Schlaepfer, M. Presta, and M. Rusnati {alpha}v{beta}3-integrin-dependent activation of focal adhesion kinase mediates NF-{kappa}B activation and motogenic activity by HIV-1 Tat in endothelial cells J. Cell Sci., September 1, 2005; 118(17): 3949 - 3958. [Abstract] [Full Text] [PDF]

				E. Kurenova, L.-H. Xu, X. Yang, A. S. Baldwin Jr., R. J. Craven, S. K. Hanks, Z.-g. Liu, and W. G. Cance Focal Adhesion Kinase Suppresses Apoptosis by Binding to the Death Domain of Receptor-Interacting Protein Mol. Cell. Biol., May 15, 2004; 24(10): 4361 - 4371. [Abstract] [Full Text] [PDF]