The Transcriptional Activity of NF-κB Is Regulated by the IκB-Associated PKAc Subunit through a Cyclic AMP–Independent Mechanism

Department of Molecular Biophysics and Biochemistry, Howard Hughes Medical Institute, Yale University School of Medicine, New Haven, Connecticut 06520, USA.
Cell (Impact Factor: 32.24). 06/1997; 89(3):413-24. DOI: 10.1016/S0092-8674(00)80222-6
Source: PubMed


Stimulation of cells with inducers of NF-kappaB such as LPS and IL-1 leads to the degradation of IkappaB-alpha and IkappaB-beta proteins and translocation of NF-kappaB to the nucleus. We now demonstrate that, besides the physical partitioning of inactive NF-kappaB to the cytosol, the transcriptional activity of NF-kappaB is regulated through phosphorylation of NF-kappaB p65 by protein kinase A (PKA). The catalytic subunit of PKA (PKAc) is maintained in an inactive state through association with IkappaB-alpha or IkappaB-beta in an NF-kappaB-IkappaB-PKAc complex. Signals that cause the degradation of IkappaB 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-kappaB activity.

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Available from: Hediye Erdjument-Bromage, Apr 29, 2015
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