Publication Date:
2001-08-25
Description:
In mammals, the canonical nuclear factor kappaB (NF-kappaB) signaling pathway activated in response to infections is based on degradation of IkappaB inhibitors. This pathway depends on the IkappaB kinase (IKK), which contains two catalytic subunits, IKKalpha and IKKbeta. IKKbeta is essential for inducible IkappaB phosphorylation and degradation, whereas IKKalpha is not. Here we show that IKKalpha is required for B cell maturation, formation of secondary lymphoid organs, increased expression of certain NF-kappaB target genes, and processing of the NF-kappaB2 (p100) precursor. IKKalpha preferentially phosphorylates NF-kappaB2, and this activity requires its phosphorylation by upstream kinases, one of which may be NF-kappaB-inducing kinase (NIK). IKKalpha is therefore a pivotal component of a second NF-kappaB activation pathway based on regulated NF-kappaB2 processing rather than IkappaB degradation.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Senftleben, U -- Cao, Y -- Xiao, G -- Greten, F R -- Krahn, G -- Bonizzi, G -- Chen, Y -- Hu, Y -- Fong, A -- Sun, S C -- Karin, M -- AI434477/AI/NIAID NIH HHS/ -- AI45045/AI/NIAID NIH HHS/ -- ESO4151/ES/NIEHS NIH HHS/ -- New York, N.Y. -- Science. 2001 Aug 24;293(5534):1495-9.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Laboratory of Gene Regulation and Signal Transduction, Department of Pharmacology, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/11520989" target="_blank"〉PubMed〈/a〉
Keywords:
Animals
;
B-Lymphocytes/immunology/*physiology
;
Bone Marrow Cells/metabolism
;
Evolution, Molecular
;
Female
;
Gene Expression Regulation
;
Germinal Center
;
I-kappa B Kinase
;
I-kappa B Proteins/metabolism
;
Immunoglobulin D/analysis
;
Lipopolysaccharides/pharmacology
;
Lymph Nodes/cytology/immunology
;
Lymphoid Tissue/*physiology
;
Mice
;
Mice, Inbred C57BL
;
Mice, Knockout
;
NF-kappa B/*metabolism
;
NF-kappa B p52 Subunit
;
Phosphorylation
;
Protein Processing, Post-Translational
;
Protein-Serine-Threonine Kinases/*metabolism
;
Radiation Chimera
;
Recombinant Proteins/metabolism
;
*Signal Transduction
;
Spleen/cytology/immunology
;
Transcription, Genetic
;
Transfection
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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