Publication Date:
2001-03-17
Description:
The role of NF-kappaB-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-kappaB 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-kappaB in a receptor-restricted manner.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Yin, L -- Wu, L -- Wesche, H -- Arthur, C D -- White, J M -- Goeddel, D V -- Schreiber, R D -- New York, N.Y. -- Science. 2001 Mar 16;291(5511):2162-5.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Center for Immunology, Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/11251123" target="_blank"〉PubMed〈/a〉
Keywords:
Animals
;
Antibodies, Monoclonal
;
B-Lymphocytes/metabolism
;
Cells, Cultured
;
DNA/metabolism
;
Fibroblasts/metabolism
;
Gene Targeting
;
Genes, Reporter
;
Interleukin-1/metabolism/pharmacology
;
Ligands
;
Lymphoid Tissue/abnormalities
;
Lymphotoxin beta Receptor
;
Mice
;
Mice, Inbred C57BL
;
NF-kappa B/genetics/*metabolism
;
Protein-Serine-Threonine Kinases/genetics/*metabolism
;
Receptors, Tumor Necrosis Factor/immunology/*metabolism
;
Signal Transduction
;
*Transcription, Genetic
;
Tumor Necrosis Factor-alpha/metabolism/pharmacology
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
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