Fiona Yull

Last active: 3/21/2018

Differential serine phosphorylation regulates IkappaB-alpha inactivation.

Chen CL, Yull FE, Kerr LD
Biochem Biophys Res Commun. 1999 257 (3): 798-806

PMID: 10208863 · DOI:10.1006/bbrc.1999.0548

NF-kappaB is a ubiquitous transcription factor involved in the signal transduction mechanisms of the immune response, acute phase reactions, and viral infections. NF-kappaB proteins are retained in the cytoplasm by association with an inhibitor, termed IkappaB. Studies on the regulation of mammalian IkappaB-alpha 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 IkappaB-alpha are phosphorylation targets leading to inactivation of IkappaB-alpha upon stimulation. In addition, we show differential roles for these two serines. Mutation of serine 40 to alanine blocks all stimuli tested (TNF-alpha, phorbol ester, and anti-CD3 and anti-CD28), leading to NF-kappaB activation, while mutation of serine 36 to alanine attenuates only certain transduced signals (PMA, TNF-alpha). These novel findings support the hypothesis that the amino-terminal phosphoserine residues of avian IkappaB-alpha differentially mediate NF-kappaB signal transduction pathways and activation by distinct signals, thereby resulting in the activation NF-kappaB.

Copyright 1999 Academic Press.

MeSH Terms (24)

Amino Acid Substitution Animals Antigens, CD Apoptosis Birds Cell Line Conserved Sequence DNA DNA-Binding Proteins Drosophila melanogaster Genes, Reporter Humans I-kappa B Proteins Jurkat Cells NF-kappa B NF-KappaB Inhibitor alpha Phosphorylation Promoter Regions, Genetic Protein Binding Serine Signal Transduction Tetradecanoylphorbol Acetate Transfection Tumor Necrosis Factor-alpha

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