Defective lymphotoxin-beta receptor-induced NF-kappaB transcriptional activity in NIK-deficient mice.
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.
Center for Immunology, Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA.
L
L
Yin
L
L
Wu
H
H
Wesche
C D
CD
Arthur
J M
JM
White
D V
DV
Goeddel
R D
RD
Schreiber
D000818:Animals; D000911:Antibodies, Monoclonal; D001402:B-Lymphocytes / Q000378:metabolism; D002478:Cells, Cultured; D004247:DNA / Q000378:metabolism; D005347:Fibroblasts / Q000378:metabolism; D018390:Gene Targeting; D017930:Genes, Reporter; D007375:Interleukin-1 / Q000378:metabolism / Q000494:pharmacology; D008024:Ligands; D008221:Lymphoid Tissue / Q000002:abnormalities; D053259:Lymphotoxin beta Receptor; D051379:Mice; D008810:Mice, Inbred C57BL; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D018124:Receptors, Tumor Necrosis Factor / Q000276:immunology / Q000378:metabolism*; D015398:Signal Transduction; D014158:Transcription, Genetic; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism / Q000494:pharmacology; D000097782:NF-kappaB-Inducing Kinase
D000911:Antibodies, Monoclonal; D004247:DNA; D007375:Interleukin-1; D008024:Ligands; D053259:Lymphotoxin beta Receptor; D016328:NF-kappa B; D017346:Protein Serine-Threonine Kinases; D018124:Receptors, Tumor Necrosis Factor; D014409:Tumor Necrosis Factor-alpha; D000097782:NF-kappaB-Inducing Kinase; C505699:Ltbr protein, mouse