Phosphorylation of human I kappa B-alpha on serines 32 and 36 controls I kappa B-alpha proteolysis and NF-kappa B activation in response to diverse stimuli
| Autor: | S. Wilk, K. N. Schmidt, E. B.-M. Traenckner, Patrick A. Baeuerle, T. Henkel, Heike L. Pahl |
|---|---|
| Rok vydání: | 1995 |
| Předmět: |
Transcriptional Activation
Proteasome Endopeptidase Complex Recombinant Fusion Proteins Molecular Sequence Data Biology General Biochemistry Genetics and Molecular Biology chemistry.chemical_compound Transactivation NF-KappaB Inhibitor alpha Ethers Cyclic Multienzyme Complexes Okadaic Acid Phosphoprotein Phosphatases Serine Humans Point Mutation Enzyme Inhibitors Phosphorylation Molecular Biology Base Sequence General Immunology and Microbiology Tumor Necrosis Factor-alpha Kinase General Neuroscience NF-kappa B Okadaic acid NFKB1 Molecular biology DNA-Binding Proteins Cysteine Endopeptidases chemistry Phorbol Tetradecanoylphorbol Acetate I-kappa B Proteins Tumor necrosis factor alpha Oligopeptides Kappa Research Article HeLa Cells |
| Zdroj: | The EMBO Journal. 14:2876-2883 |
| ISSN: | 0261-4189 |
| DOI: | 10.1002/j.1460-2075.1995.tb07287.x |
| Popis: | Post-translational activation of the higher eukaryotic transcription factor NF-kappa B requires both phosphorylation and proteolytic degradation of the inhibitory subunit I kappa B-alpha. Inhibition of proteasome activity can stabilize an inducibly phosphorylated form of I kappa B-alpha in intact cells, suggesting that phosphorylation targets the protein for degradation. In this study, we have identified serines 32 and 36 in human I kappa B-alpha as essential for the control of I kappa B-alpha stability and the activation of NF-kappa B in HeLa cells. A point mutant substituting serines 32 and 36 by alanine residues was no longer phosphorylated in response to okadaic acid (OA) stimulation. This and various other Ser32 and Ser36 mutants behaved as potent dominant negative I kappa B proteins attenuating kappa B-dependent transactivation in response to OA, phorbol 12-myristate 13-acetate (PMA) and tumor necrosis factor-alpha (TNF). While both endogenous and transiently expressed wild-type I kappa B-alpha were proteolytically degraded in response to PMA and TNF stimulation of cells, the S32/36A mutant of I kappa B-alpha remained largely intact under these conditions. Our data suggest that such diverse stimuli as OA, TNF and PMA use the same kinase system to phosphorylate and thereby destabilize I kappa B-alpha, leading to NF-kappa B activation. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|