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Science 16 March 2001:
Vol. 291. no. 5511, pp. 2162 - 2165
DOI: 10.1126/science.1058453
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Reports

Defective Lymphotoxin-beta Receptor-Induced NF-kappa B Transcriptional Activity in NIK-Deficient Mice

Li Yin,1 Lin Wu,2 Holger Wesche,2 Cora D. Arthur,1 J. Michael White,1 David V. Goeddel,2 Robert D. Schreiber1*

The role of NF-kappa B-inducing kinase (NIK) in cytokine signaling remains controversial. To identify the physiologic functions of NIK, we disrupted the NIK locus by gene targeting. Although NIK-/- mice displayed abnormalities in both lymphoid tissue development and antibody responses, NIK-/- cells manifested normal NF-kappa B DNA binding activity when treated with a variety of cytokines, including tumor necrosis factor (TNF), interleukin-1 (IL-1), and lymphotoxin-beta (LTbeta ). However, NIK was selectively required for gene transcription induced through ligation of LTbeta receptor but not TNF receptors. These results reveal that NIK regulates the transcriptional activity of NF-kappa B in a receptor-restricted manner.

1 Center for Immunology, Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA.
2 Tularik Inc., 2 Corporate Drive, South San Francisco, CA 94080, USA.
*   To whom correspondence should be addressed. E-mail: schreiber{at}immunology.wustl.edu

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Reactive Oxygen Species Are Downstream Products of TRAF-mediated Signal Transduction.
N. S. Chandel, P. T. Schumacker, and R. H. Arch (2001)
J. Biol. Chem. 276, 42728-42736
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IRAK-mediated Translocation of TRAF6 and TAB2 in the Interleukin-1-induced Activation of NFkappa B.
Y. Qian, M. Commane, J. Ninomiya-Tsuji, K. Matsumoto, and X. Li (2001)
J. Biol. Chem. 276, 41661-41667
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Requirement of NF-{kappa}B/Rel for the development of hair follicles and other epidermal appendices.
R. Schmidt-Ullrich, T. Aebischer, J. Hulsken, W. Birchmeier, U. Klemm, and C. Scheidereit (2001)
Development 128, 3843-3853
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NF-{kappa}B signaling pathways in mammalian and insect innate immunity.
N. Silverman and T. Maniatis (2001)
Genes & Dev. 15, 2321-2342
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Dbl and the Rho GTPases Activate NFkappa B by Ikappa B Kinase (IKK)-dependent and IKK-independent Pathways.
M. S. Cammarano and A. Minden (2001)
J. Biol. Chem. 276, 25876-25882
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Critical Roles of TRAF2 and TRAF5 in Tumor Necrosis Factor-induced NF-kappa B Activation and Protection from Cell Death.
K. Tada, T. Okazaki, S. Sakon, T. Kobarai, K. Kurosawa, S. Yamaoka, H. Hashimoto, T. W. Mak, H. Yagita, K. Okumura, et al. (2001)
J. Biol. Chem. 276, 36530-36534
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