The transcriptional activity of NF-kappaB is regulated by the IkappaB-associated PKAc subunit through a cyclic AMP-independent mechanism

Cell. 1997 May 2;89(3):413-24. doi: 10.1016/s0092-8674(00)80222-6.


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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adenosine Triphosphate / metabolism
  • Amino Acid Sequence
  • Animals
  • Calpain / antagonists & inhibitors
  • Cell Nucleus / metabolism
  • Cyclic AMP / physiology*
  • Cyclic AMP-Dependent Protein Kinases / chemistry
  • Cyclic AMP-Dependent Protein Kinases / isolation & purification
  • Cyclic AMP-Dependent Protein Kinases / metabolism*
  • Cytosol / chemistry
  • DNA-Binding Proteins / metabolism
  • Enzyme Inhibitors / pharmacology
  • Gene Expression Regulation, Enzymologic / physiology
  • Lipopolysaccharides / pharmacology
  • Lung / chemistry
  • Molecular Sequence Data
  • NF-kappa B / genetics*
  • NF-kappa B / metabolism
  • Phosphorylation
  • Protein Binding / physiology
  • Protein Structure, Tertiary
  • Rabbits
  • Transcriptional Activation / drug effects
  • Transcriptional Activation / physiology*


  • DNA-Binding Proteins
  • Enzyme Inhibitors
  • Lipopolysaccharides
  • NF-kappa B
  • Adenosine Triphosphate
  • Cyclic AMP
  • Cyclic AMP-Dependent Protein Kinases
  • Calpain