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| PHOSPHORYLATION OF HUMAN I-KAPPA-B-ALPHA ON SERINE-32 AND SERINE-36 CONTROLS I-KAPPA-B-ALPHA PROTEOLYSIS AND NF-KAPPA-B ACTIVATION IN RESPONSE TO DIVERSE STIMULI |
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| Author(s): TRAENCKNER EBM, PAHL HL, HENKEL T, SCHMIDT KN, WILK S, BAEUERLE PA |
| Source: EMBO JOURNAL Volume: 14 Issue: 12 Pages: 2876-2883 Published: JUN 15 1995 |
| Times Cited: 722 References: 56 |
| Abstract: 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. |
| Document Type: Article |
| Language: English |
Addresses:
1. UNIV FREIBURG, INST BIOCHEM, D-79104 FREIBURG, GERMANY
2. CUNY MT SINAI SCH MED, DEPT PHARMACOL, NEW YORK, NY 10029 USA |
| Publisher: OXFORD UNIV PRESS UNITED KINGDOM, WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP |
| Subject Category: Biochemistry & Molecular Biology; Cell Biology |
| IDS Number: RF900 |
| ISSN: 0261-4189 |
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