IKKepsilon is part of a novel PMA-inducible IkappaB kinase complex.
Here we report the identification of a novel PMA-inducible IkappaB kinase complex, distinct from the well-characterized high-molecular weight IkappaB kinase complex containing IKKalpha, IKKbeta, and IKKgamma. We have characterized one kinase from this complex, which we designate IKKepsilon. Although recombinant IKKepsilon directly phosphorylates only serine 36 of IKBalpha, the PMA-activated endogenous IKKepsilon complex phosphorylates both critical serine residues. Remarkably, this activity is due to the presence of a distinct kinase in this complex. A dominant-negative mutant of IKKepsilon blocks induction of NF-kappaB by both PMA and activation of the T cell receptor but has no effect on the activation of NF-KB by TNFalpha or IL-1. These observations indicate that the activation of NF-kappaB requires multiple distinct IkappaB kinase complexes, which respond to both overlapping and discrete signaling pathways.
Peters
R T
RT
Department of Molecular and Cellular Biology, Harvard University, Cambridge, Massachusetts 02138, USA.
Liao
S M
SM
Maniatis
T
T
D000595:Amino Acid Sequence; D004790:Enzyme Induction; D006367:HeLa Cells; D006801:Humans; D051550:I-kappa B Kinase; D020672:I-kappa B Proteins / Q000378:metabolism*; D007375:Interleukin-1 / Q000494:pharmacology; D019169:Jurkat Cells; D008969:Molecular Sequence Data; D010766:Phosphorylation; D015221:Potassium Channels / Q000302:isolation & purification; D024681:Potassium Channels, Calcium-Activated; D011485:Protein Binding; D011487:Protein Conformation; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D012694:Serine / Q000378:metabolism; D015398:Signal Transduction; D051640:Small-Conductance Calcium-Activated Potassium Channels; D013379:Substrate Specificity; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D020672:I-kappa B Proteins; D007375:Interleukin-1; D015221:Potassium Channels; D024681:Potassium Channels, Calcium-Activated; D011948:Receptors, Antigen, T-Cell; D051640:Small-Conductance Calcium-Activated Potassium Channels; D014409:Tumor Necrosis Factor-alpha; D012694:Serine; D017346:Protein Serine-Threonine Kinases; C496559:CHUK protein, human; D051550:I-kappa B Kinase; C496560:IKBKB protein, human; C496565:IKBKE protein, human; D013755:Tetradecanoylphorbol Acetate