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IKKepsilon is part of a novel PMA-inducible IkappaB kinase complex.
- Source :
-
Molecular cell [Mol Cell] 2000 Mar; Vol. 5 (3), pp. 513-22. - Publication Year :
- 2000
-
Abstract
- 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.
- Subjects :
- Amino Acid Sequence
Enzyme Induction
HeLa Cells
Humans
I-kappa B Kinase
Interleukin-1 pharmacology
Jurkat Cells
Molecular Sequence Data
Phosphorylation
Potassium Channels isolation & purification
Protein Binding
Protein Conformation
Protein Serine-Threonine Kinases genetics
Receptors, Antigen, T-Cell metabolism
Sequence Homology, Amino Acid
Serine metabolism
Signal Transduction
Small-Conductance Calcium-Activated Potassium Channels
Substrate Specificity
Tumor Necrosis Factor-alpha pharmacology
I-kappa B Proteins metabolism
Potassium Channels, Calcium-Activated
Protein Serine-Threonine Kinases metabolism
Tetradecanoylphorbol Acetate pharmacology
Subjects
Details
- Language :
- English
- ISSN :
- 1097-2765
- Volume :
- 5
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- Molecular cell
- Publication Type :
- Academic Journal
- Accession number :
- 10882136
- Full Text :
- https://doi.org/10.1016/s1097-2765(00)80445-1