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

J. Biol. Chem., Vol. 281, Issue 33, 23525-23532, August 18, 2006

This Article Full Text Full Text (PDF) All Versions of this Article: 281/33/23525    most recent M601487200v1 Submit a Letter to Editor Alert me when this article is cited Alert me when eLetters are posted 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 Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Lin, Y. Articles by Liu, Z.-g. Search for Related Content PubMed PubMed Citation Articles by Lin, Y. Articles by Liu, Z.-g. Social Bookmarking                      What's this?

The Essential Role of the Death Domain Kinase Receptor-interacting Protein in Insulin Growth Factor-I-induced c-Jun N-terminal Kinase Activation^*

Yong Lin¹, Qingfeng Yang², Xia Wang, and Zheng-gang Liu

From the Molecular Biology and Lung Cancer Program, Lovelace Respiratory Research Institute, Albuquerque, New Mexico 87108 and the Cell and Cancer Biology Branch, NCI, National Institutes of Health, Bethesda, Maryland 20892

Insulin-like growth factor I (IGF-I) plays an important role in cell survival, proliferation, and differentiation. Diverse kinases, including AKT/protein kinase B, extracellular signal-regulated kinase (ERK), and c-Jun N-terminal kinase (JNK), can be activated by IGF-I. Here, we show that the receptor-interacting protein (RIP), a key mediator of tumor necrosis factor-induced NF-B and JNK activation, plays a key role in IGF-I receptor signaling. IGF-I induced a robust JNK activation in wild type but not RIP null (RIP–/–) mouse embryonic fibroblast cells. Reconstitution of RIP expression in the RIP–/– cells restored the induction of JNK by IGF-I, suggesting that RIP is essential in IGF-I-induced JNK activation. Reconstitution experiments with different RIP mutants further revealed that the death domain and the kinase activity of RIP are not required for IGF-I-induced JNK activation. Interestingly, the AKT and ERK activation by IGF-I was normal in RIP–/– cells. The phosphatidylinositol 3-kinase inhibitor, wortmannin, did not affect IGF-I-induced JNK activation. These results agree with previous studies showing that the IGF-I-induced JNK activation pathway is distinct from that of ERK and AKT activation. Additionally, physical interaction of ectopically expressed RIP and IGF-IR was detected by co-immunoprecipitation assays. More importantly, RIP was recruited to the IGF-I receptor complex during IGF-I-induced signaling. Furthermore, we found that IGF-I-induced cell proliferation was impaired in RIP–/– cells. Taken together, our results indicate that RIP, a key factor in tumor necrosis factor signaling, also plays a pivotal role in IGF-I-induced JNK activation and cell proliferation.

Received for publication, February 15, 2006 , and in revised form, June 20, 2006.

^* 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.

² Current address: Dept. of Anatomy, Physiology, and Genetics, Institute for Molecular Medicine, Uniformed Services University School of Medicine, Uniformed Services University of the Health Sciences, Bethesda, MD 20814.

¹ To whom correspondence should be addressed: Molecular Biology and Lung Cancer Program, Lovelace Respiratory Research Institute, 2425 Ridgecrest Dr., SE, Albuquerque, NM 87108. Tel.: 505-348-9645; Fax: 505-348-9400; E-mail: ylin{at}lrri.org.

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

This article has been cited by other articles:

				L. Bai, W. Chen, W. Chen, X. Wang, H. Tang, and Y. Lin IKK{beta}-mediated nuclear factor-{kappa}B activation attenuates smac mimetic-induced apoptosis in cancer cells Mol. Cancer Ther., June 1, 2009; 8(6): 1636 - 1645. [Abstract] [Full Text] [PDF]

				C. Nevado, M. Benito, and A. M. Valverde Role of Insulin Receptor and Balance in Insulin Receptor Isoforms A and B in Regulation of Apoptosis in Simian Virus 40-immortalized Neonatal Hepatocytes Mol. Biol. Cell, March 1, 2008; 19(3): 1185 - 1198. [Abstract] [Full Text] [PDF]

				W. Chen, X. Wang, J. Zhuang, L. Zhang, and Y. Lin Induction of death receptor 5 and suppression of survivin contribute to sensitization of TRAIL-induced cytotoxicity by quercetin in non-small cell lung cancer cells Carcinogenesis, October 1, 2007; 28(10): 2114 - 2121. [Abstract] [Full Text] [PDF]

				W. Ju, X. Wang, H. Shi, W. Chen, S. A. Belinsky, and Y. Lin A Critical Role of Luteolin-Induced Reactive Oxygen Species in Blockage of Tumor Necrosis Factor-Activated Nuclear Factor-{kappa}B Pathway and Sensitization of Apoptosis in Lung Cancer Cells Mol. Pharmacol., May 1, 2007; 71(5): 1381 - 1388. [Abstract] [Full Text] [PDF]