The transcriptional activity of NF-κB is regulated by the IκB- associated PKAc subunit through a cyclic AMP-independent mechanism Journal Article


Authors: Zhong, H.; Su Yang, H.; Erdjument-Bromage, H.; Tempst, P.; Ghosh, S.
Article Title: The transcriptional activity of NF-κB is regulated by the IκB- associated PKAc subunit through a cyclic AMP-independent mechanism
Abstract: Stimulation of cells with inducers of NF-κB such as LPS and IL-1 leads to the degradation of IκB-α and IκB-β proteins and translocation of NF- κB to the nucleus. We now demonstrate that, besides the physical partitioning of inactive NF-κB to the cytosol, the transcriptional activity of NF-κB is regulated through phosphorylation of NF-κB p65 by protein kinase A (PKA). The catalytic subunit of PKA (PKAc) is maintained in an inactive state through association with IκB-α or IκB-̄ in an NF-κB- IκB-PKAc complex. Signals that cause the degradation of IκB result in activation of PKAc in a cAMP-independent manner and the subsequent phosphorylation of p65. Therefore, this pathway represents a novel mechanism for the cAMP-independent activation of PKA and the regulation of NF-≃B activity.
Keywords: controlled study; protein phosphorylation; dna-binding proteins; nonhuman; animal cell; animals; protein binding; transcription factor; immunoglobulin enhancer binding protein; enzyme activation; enzyme activity; phosphorylation; animalia; enzyme regulation; transcription regulation; amino acid sequence; molecular sequence data; enzyme inhibitors; nf-kappa b; lung; cyclic amp; lipopolysaccharide; protein structure, tertiary; cell nucleus; adenosine triphosphate; cytosol; synaptotagmin; regulator protein; enzyme active site; interleukin 1; gene expression regulation, enzymologic; cyclic amp dependent protein kinase; cyclic amp-dependent protein kinases; rabbits; lipopolysaccharides; rabbit; trans-activation (genetics); ankyrin; oryctolagus cuniculus; calpain; priority journal; article
Journal Title: Cell
Volume: 89
Issue: 3
ISSN: 0092-8674
Publisher: Cell Press  
Date Published: 1997-05-02
Start Page: 413
End Page: 424
Language: English
DOI: 10.1016/s0092-8674(00)80222-6
PUBMED: 9150141
PROVIDER: scopus
DOI/URL:
Notes: Article -- Export Date: 17 March 2017 -- Source: Scopus
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  1. Paul J Tempst
    324 Tempst