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Science 31 October 1997:
Vol. 278. no. 5339, pp. 866 - 870
DOI: 10.1126/science.278.5339.866
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Reports

Ikappa B Kinase-beta : NF-kappa B Activation and Complex Formation with Ikappa B Kinase-alpha and NIK

John D. Woronicz, Xiong Gao, Zhaodan Cao, Mike Rothe, David V. Goeddel *

Activation of the transcription factor nuclear factor kappa B (NF-kappa B) by inflammatory cytokines requires the successive action of NF-kappa B-inducing kinase (NIK) and Ikappa B kinase-alpha (IKK-alpha ). A widely expressed protein kinase was identified that is 52 percent identical to IKK-alpha . Ikappa B kinase-beta (IKK-beta ) activated NF-kappa B when overexpressed and phosphorylated serine residues 32 and 36 of Ikappa B-alpha and serines 19 and 23 of Ikappa B-beta . The activity of IKK-beta was stimulated by tumor necrosis factor and interleukin-1 treatment. IKK-alpha and IKK-beta formed heterodimers that interacted with NIK. Overexpression of a catalytically inactive form of IKK-beta blocked cytokine-induced NF-kappa B activation. Thus, an active Ikappa B kinase complex may require three distinct protein kinases.

Tularik, Two Corporate Drive, South San Francisco, CA 94080, USA.
*   To whom correspondence should be addressed. E-mail: goeddel{at}tularik.com

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   Abstract »    Full Text »    PDF »
CD28 delivers a unique signal leading to the selective recruitment of RelA and p52 NF-{kappa}B subunits on IL-8 and Bcl-xL gene promoters.
B. Marinari, A. Costanzo, V. Marzano, E. Piccolella, and L. Tuosto (2004)
PNAS 101, 6098-6103
   Abstract »    Full Text »    PDF »
ZNF216 Is an A20-like and I{kappa}B Kinase {gamma}-Interacting Inhibitor of NF{kappa}B Activation.
J. Huang, L. Teng, L. Li, T. Liu, L. Li, D. Chen, L.-G. Xu, Z. Zhai, and H.-B. Shu (2004)
J. Biol. Chem. 279, 16847-16853
   Abstract »    Full Text »    PDF »
Review: Molecular mechanisms of endotoxin tolerance.
Hongkuan Fan and J. A. Cook (2004)
Innate Immunity 10, 71-84
   Abstract »    PDF »
Toll-like receptor 3-mediated activation of NF-{kappa}B and IRF3 diverges at Toll-IL-1 receptor domain-containing adapter inducing IFN-{beta}.
Z. Jiang, T. W. Mak, G. Sen, and X. Li (2004)
PNAS 101, 3533-3538
   Abstract »    Full Text »    PDF »
RICK Activates a NF-{kappa}B-dependent Anti-human Cytomegalovirus Response.
J. Eickhoff, M. Hanke, M. Stein-Gerlach, T. P. Kiang, K. Herzberger, P. Habenberger, S. Muller, B. Klebl, M. Marschall, T. Stamminger, et al. (2004)
J. Biol. Chem. 279, 9642-9652
   Abstract »    Full Text »    PDF »
Immunosuppressive Activity of Endovanilloids: N-Arachidonoyl-Dopamine Inhibits Activation of the NF-{kappa}B, NFAT, and Activator Protein 1 Signaling Pathways.
R. Sancho, A. Macho, L. de La Vega, M. A. Calzado, B. L. Fiebich, G. Appendino, and E. Munoz (2004)
J. Immunol. 172, 2341-2351
   Abstract »    Full Text »    PDF »
Nuclear Role of I{kappa}B Kinase-{gamma}/NF-{kappa}B Essential Modulator (IKK{gamma}/NEMO) in NF-{kappa}B-dependent Gene Expression.
U. N. Verma, Y. Yamamoto, S. Prajapati, and R. B. Gaynor (2004)
J. Biol. Chem. 279, 3509-3515
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Cell Type-specific Expression of the I{kappa}B Kinases Determines the Significance of Phosphatidylinositol 3-Kinase/Akt Signaling to NF-{kappa}B Activation.
J. A. Gustin, O. N. Ozes, H. Akca, R. Pincheira, L. D. Mayo, Q. Li, J. R. Guzman, C. K. Korgaonkar, and D. B. Donner (2004)
J. Biol. Chem. 279, 1615-1620
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Protein Phosphatase 2C{beta} Association with the I{kappa}B Kinase Complex Is Involved in Regulating NF-{kappa}B Activity.
S. Prajapati, U. Verma, Y. Yamamoto, Y. T. Kwak, and R. B. Gaynor (2004)
J. Biol. Chem. 279, 1739-1746
   Abstract »    Full Text »    PDF »
Distinct Domains in the SHP-2 Phosphatase Differentially Regulate Epidermal Growth Factor Receptor/NF-{kappa}B Activation through Gab1 in Glioblastoma Cells.
G. S. Kapoor, Y. Zhan, G. R. Johnson, and D. M. O'Rourke (2004)
Mol. Cell. Biol. 24, 823-836
   Abstract »    Full Text »    PDF »
Tumor Necrosis Factor-{alpha} Inhibits Endothelial Nitric-oxide Synthase Gene Promoter Activity in Bovine Aortic Endothelial Cells.
H. D. I. Anderson, D. Rahmutula, and D. G. Gardner (2004)
J. Biol. Chem. 279, 963-969
   Abstract »    Full Text »    PDF »
NF-{kappa}B Promotes Survival during Mitotic Cell Cycle Arrest.
P. Mistry, K. Deacon, S. Mistry, J. Blank, and R. Patel (2004)
J. Biol. Chem. 279, 1482-1490
   Abstract »    Full Text »    PDF »
Two Carboxyl-terminal Activation Regions of Epstein-Barr Virus Latent Membrane Protein 1 Activate NF-{kappa}B through Distinct Signaling Pathways in Fibroblast Cell Lines.
N. Saito, G. Courtois, A. Chiba, N. Yamamoto, T. Nitta, N. Hironaka, M. Rowe, N. Yamamoto, and S. Yamaoka (2003)
J. Biol. Chem. 278, 46565-46575
   Abstract »    Full Text »    PDF »
Direct Inhibition of NF-{kappa}B Blocks Bone Erosion Associated with Inflammatory Arthritis.
J. C. Clohisy, B. C. Roy, C. Biondo, E. Frazier, D. Willis, S. L. Teitelbaum, and Y. Abu-Amer (2003)
J. Immunol. 171, 5547-5553
   Abstract »    Full Text »    PDF »
Identification of NAP1, a Regulatory Subunit of I{kappa}B Kinase-Related Kinases That Potentiates NF-{kappa}B Signaling.
F. Fujita, Y. Taniguchi, T. Kato, Y. Narita, A. Furuya, T. Ogawa, H. Sakurai, T. Joh, M. Itoh, M. Delhase, et al. (2003)
Mol. Cell. Biol. 23, 7780-7793
   Abstract »    Full Text »    PDF »
Roles for Homotypic Interactions and Transautophosphorylation in I{kappa}B Kinase (IKK{beta}) Activation.
E. D. Tang, N. Inohara, C.-Y. Wang, G. Nunez, and K.-L. Guan (2003)
J. Biol. Chem. 278, 38566-38570
   Abstract »    Full Text »    PDF »
Protein Kinase C{alpha} (PKC{alpha}) Acts Upstream of PKC{theta} To Activate I{kappa}B Kinase and NF-{kappa}B in T Lymphocytes.
S. A. Trushin, K. N. Pennington, E. M. Carmona, S. Asin, D. N. Savoy, D. D. Billadeau, and C. V. Paya (2003)
Mol. Cell. Biol. 23, 7068-7081
   Abstract »    Full Text »    PDF »
Inhibition of Tumor Necrosis Factor-{alpha}-Induced SHP-2 Phosphatase Activity by Shear Stress: A Mechanism to Reduce Endothelial Inflammation.
N. Lerner-Marmarosh, M. Yoshizumi, W. Che, J. Surapisitchat, H. Kawakatsu, M. Akaike, B. Ding, Q. Huang, C. Yan, B. C. Berk, et al. (2003)
Arterioscler Thromb Vasc Biol 23, 1775-1781
   Abstract »    Full Text »    PDF »
A Role for NF-{kappa}B Essential Modifier/I{kappa}B Kinase-{gamma} (NEMO/IKK{gamma}) Ubiquitination in the Activation of the I{kappa}B Kinase Complex by Tumor Necrosis Factor-{alpha}.
E. D. Tang, C.-Y. Wang, Y. Xiong, and K.-L. Guan (2003)
J. Biol. Chem. 278, 37297-37305
   Abstract »    Full Text »    PDF »
KSHV vFLIP binds to IKK-{gamma} to activate IKK.
N. Field, W. Low, M. Daniels, S. Howell, L. Daviet, C. Boshoff, and M. Collins (2003)
J. Cell Sci. 116, 3721-3728
   Abstract »    Full Text »    PDF »
PKC{zeta} participates in activation of inflammatory response induced by enteropathogenic E. coli.
S. D. Savkovic, A. Koutsouris, and G. Hecht (2003)
Am J Physiol Cell Physiol 285, C512-C521
   Abstract »    Full Text »    PDF »
TRAF2 Exerts Its Antiapoptotic Effect by Regulating the Expression of Kruppel-Like Factor LKLF.
Y. Lin, J. Ryan, J. Lewis, M. A. Wani, J. B. Lingrel, and Z.-g. Liu (2003)
Mol. Cell. Biol. 23, 5849-5856
   Abstract »    Full Text »    PDF »
RelA Control of I{kappa}B{alpha} Phosphorylation: A POSITIVE FEEDBACK LOOP FOR HIGH AFFINITY NF-{kappa}B COMPLEXES.
L. Yang, K. Ross, and E. E. Qwarnstrom (2003)
J. Biol. Chem. 278, 30881-30888
   Abstract »    Full Text »    PDF »
Helicobacter pylori Induces RANTES through Activation of NF-{kappa}B.
N. Mori, A. M. Krensky, R. Geleziunas, A. Wada, T. Hirayama, C. Sasakawa, and N. Yamamoto (2003)
Infect. Immun. 71, 3748-3756
   Abstract »    Full Text »    PDF »


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