Differential Serine Phosphorylation Regulates IκB-α Inactivation

NF-κB is a ubiquitous transcription factor involved in the signal transduction mechanisms of the immune response, acute phase reactions, and viral infections. NF-κB proteins are retained in the cytoplasm by association with an inhibitor, termed IκB. Studies on the regulation of mammalian IκB-α have...

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Bibliographic Details
Published in:Biochemical and biophysical research communications 1999-04, Vol.257 (3), p.798-806
Main Authors: Chen, Chih-Li, Yull, Fiona E., Kerr, Lawrence D.
Format: Article
Language:English
Subjects:
IκB-α
NF-κB
T cell activation
TNF-α
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Summary:NF-κB is a ubiquitous transcription factor involved in the signal transduction mechanisms of the immune response, acute phase reactions, and viral infections. NF-κB proteins are retained in the cytoplasm by association with an inhibitor, termed IκB. Studies on the regulation of mammalian IκB-α have revealed that two amino-terminal conserved phosphoserines are the target sites of incoming signals. We report that the corresponding amino-terminal phosphoserines of avian IκB-α are phosphorylation targets leading to inactivation of IκB-α upon stimulation. In addition, we show differential roles for these two serines. Mutation of serine 40 to alanine blocks all stimuli tested (TNF-α, phorbol ester, and anti-CD3 and anti-CD28), leading to NF-κB activation, while mutation of serine 36 to alanine attenuates only certain transduced signals (PMA, TNF-α). These novel findings support the hypothesis that the amino-terminal phosphoserine residues of avian IκB-α differentially mediate NF-κB signal transduction pathways and activation by distinct signals, thereby resulting in the activation NF-κB.
ISSN:0006-291X
1090-2104
DOI:10.1006/bbrc.1999.0548