JBC

HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     

Originally published In Press as doi:10.1074/jbc.M001039200 on March 9, 2000
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
275/19/14752    most recent
M001039200v1
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 PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Kwak, Y. T.
Right arrow Articles by Gaynor, R. B.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Kwak, Y. T.
Right arrow Articles by Gaynor, R. B.
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?

J Biol Chem, Vol. 275, Issue 19, 14752-14759, May 12, 2000

Analysis of Domains in the IKKalpha and IKKbeta Proteins That Regulate Their Kinase Activity*

Youn Tae KwakDagger , Jun GuoDagger , Jing Shen, and Richard B. Gaynor§

From the Division of Hematology-Oncology, Department of Medicine, Harold Simmons Cancer Center, University of Texas Southwestern Medical Center, Dallas, Texas 75235-8594

The Ikappa B kinases IKKalpha and IKKbeta are critical in activating the NF-kappa B pathway. Although these proteins have a similar structure that includes kinase, leucine zipper, and helix-loop-helix domains, they exhibit marked differences in their kinase activity and functional properties. For example, IKKbeta has a 10-20-fold higher level of kinase activity for Ikappa Balpha than does IKKalpha . Furthermore, disruption of the murine IKKbeta gene, but not the IKKalpha gene, results in severe defects in activating the NF-kappa B pathway. Mice lacking IKKbeta succumb to severe hepatic apoptosis because of failure to activate the NF-kappa B pathway, whereas mice deficient in IKKalpha exhibit skin and skeletal abnormalities and an embryonic lethal phenotype. To better characterize differences in the functional properties of these kinases, hybrid IKK proteins were constructed by domain swapping, and their kinase activity was assayed. These studies demonstrated that differences in the IKKalpha and IKKbeta helix-loop-helix domains are primarily responsible for differences in their kinase activity. In contrast, their kinase and leucine zipper domains exhibited relatively conserved function. These studies further define the properties of IKKalpha and IKKbeta , which are involved in their unique regulatory roles.

* This work was supported by grants from the National Institutes of Health and the Veterans Administration.The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

Dagger These authors contributed equally to this work.

§ To whom correspondence should be addressed: Div. of Hematology-Oncology, Dept. of Medicine, U.T. Southwestern Medical Center, 5323 Harry Hines Blvd., Dallas, TX 75235-8594. Tel.: 214-648-7570; Fax: 214-648-8862; E-mail: gaynor@utsw.swmed.edu.

Copyright © 2000 by The American Society for Biochemistry and Molecular Biology, Inc.
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 page
 J. Immunol.Home page
C. Nicholas, S. Batra, M. A. Vargo, O. H. Voss, M. A. Gavrilin, M. D. Wewers, D. C. Guttridge, E. Grotewold, and A. I. Doseff
Apigenin Blocks Lipopolysaccharide-Induced Lethality In Vivo and Proinflammatory Cytokines Expression by Inactivating NF-{kappa}B through the Suppression of p65 Phosphorylation
J. Immunol., November 15, 2007; 179(10): 7121 - 7127.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
M.-Y. Park, J.-h. Moon, K.-S. Lee, H.-I. Choi, J. Chung, H. J. Hong, and E. Kim
FAF1 Suppresses I{kappa}B Kinase (IKK) Activation by Disrupting the IKK Complex Assembly
J. Biol. Chem., September 21, 2007; 282(38): 27572 - 27577.
[Abstract] [Full Text] [PDF]

Home page
 Molecular Cancer TherapeuticsHome page
S. Singh, Q. Shi, S. T. Bailey, M. J. Palczewski, A. B. Pardee, J. D. Iglehart, and D. K. Biswas
Nuclear factor-{kappa}B activation: a molecular therapeutic target for estrogen receptor-negative and epidermal growth factor receptor family receptor-positive human breast cancer
Mol. Cancer Ther., July 1, 2007; 6(7): 1973 - 1982.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
Z. Tu, S. Prajapati, K.-J. Park, N. J. Kelly, Y. Yamamoto, and R. B. Gaynor
IKK{alpha} Regulates Estrogen-induced Cell Cycle Progression by Modulating E2F1 Expression
J. Biol. Chem., March 10, 2006; 281(10): 6699 - 6706.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
Y.-T. Kwak, R. Li, C. R. Becerra, D. Tripathy, E. P. Frenkel, and U. N. Verma
I{kappa}B Kinase {alpha} Regulates Subcellular Distribution and Turnover of Cyclin D1 by Phosphorylation
J. Biol. Chem., October 7, 2005; 280(40): 33945 - 33952.
[Abstract] [Full Text] [PDF]

Home page
 Proc. Natl. Acad. Sci. USAHome page
Q. Li, Q. Lu, V. Bottero, G. Estepa, L. Morrison, F. Mercurio, and I. M. Verma
Enhanced NF-{kappa}B activation and cellular function in macrophages lacking I{kappa}B kinase 1 (IKK1)
PNAS, August 30, 2005; 102(35): 12425 - 12430.
[Abstract] [Full Text] [PDF]

Home page
 J. Leukoc. Biol.Home page
Y. Peng, M. R. Power, B. Li, and T.-J. Lin
Inhibition of IKK down-regulates antigen + IgE-induced TNF production by mast cells: a role for the IKK-I{kappa}B-NF-{kappa}B pathway in IgE-dependent mast cell activation
J. Leukoc. Biol., June 1, 2005; 77(6): 975 - 983.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
M. J. May, S. E. Larsen, J. H. Shim, L. A. Madge, and S. Ghosh
A Novel Ubiquitin-like Domain in I{kappa}B Kinase {beta} Is Required for Functional Activity of the Kinase
J. Biol. Chem., October 29, 2004; 279(44): 45528 - 45539.
[Abstract] [Full Text] [PDF]

Home page
 Genes Dev.Home page
M. S. Hayden and S. Ghosh
Signaling to NF-{kappa}B
Genes & Dev., September 15, 2004; 18(18): 2195 - 2224.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
M. Quirling, S. Page, N. Jilg, K. Plenagl, D. Peus, C. Grubmuller, M. Weingartner, C. Fischer, D. Neumeier, and K. Brand
Detection of IKK{beta}-IKK{gamma} Subcomplexes in Monocytic Cells and Characterization of Associated Signaling
J. Biol. Chem., September 3, 2004; 279(36): 37452 - 37460.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Gastrointest. Liver Physiol.Home page
P. Hilgard, M. J. Czaja, G. Gerken, and R. J. Stockert
Proapoptotic function of protein kinase CK2{alpha}" is mediated by a JNK signaling cascade
Am J Physiol Gastrointest Liver Physiol, July 1, 2004; 287(1): G192 - G201.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
S. Prajapati, U. Verma, Y. Yamamoto, Y. T. Kwak, and R. B. Gaynor
Protein Phosphatase 2C{beta} Association with the I{kappa}B Kinase Complex Is Involved in Regulating NF-{kappa}B Activity
J. Biol. Chem., January 16, 2004; 279(3): 1739 - 1746.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
M. J. May, R. B. Marienfeld, and S. Ghosh
Characterization of the Ikappa B-kinase NEMO Binding Domain
J. Biol. Chem., November 22, 2002; 277(48): 45992 - 46000.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
S. Prajapati and R. B. Gaynor
Regulation of Ikappa B Kinase (IKK)gamma /NEMO Function by IKKbeta -mediated Phosphorylation
J. Biol. Chem., June 28, 2002; 277(27): 24331 - 24339.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
C. Lamberti, K.-M. Lin, Y. Yamamoto, U. Verma, I. M. Verma, S. Byers, and R. B. Gaynor
Regulation of beta -Catenin Function by the Ikappa B Kinases
J. Biol. Chem., November 2, 2001; 276(45): 42276 - 42286.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Cell. Biol.Home page
C. Wang, M. Fu, M. D'Amico, C. Albanese, J.-N. Zhou, M. Brownlee, M. P. Lisanti, V. K. K. Chatterjee, M. A. Lazar, and R. G. Pestell
Inhibition of Cellular Proliferation through I{kappa}B Kinase-Independent and Peroxisome Proliferator-Activated Receptor {gamma}-Dependent Repression of Cyclin D1
Mol. Cell. Biol., May 1, 2001; 21(9): 3057 - 3070.
[Abstract] [Full Text]

Home page
 J. Biol. Chem.Home page
X.-H. Li, X. Fang, and R. B. Gaynor
Role of IKKgamma /NEMO in Assembly of the Ikappa B Kinase Complex
J. Biol. Chem., February 2, 2001; 276(6): 4494 - 4500.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
 All ASBMB Journals   Molecular and Cellular Proteomics 
 Journal of Lipid Research   ASBMB Today 
Copyright © 2000 by the American Society for Biochemistry and Molecular Biology.