期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：1998
卷号：95
期号：16
页码：9319-9324
DOI：10.1073/pnas.95.16.9319
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：A critical step in the signal-induced activation of the transcription factor NF-{kappa}B is the site-specific phosphorylation of its inhibitor, I{kappa}B, that targets the latter for degradation by the ubiquitin-proteasome pathway. We have previously shown that mitogen-activated protein kinase/ERK kinase kinase 1 (MEKK1) can induce both this site-specific phosphorylation of I{kappa}B at Ser-32 and Ser-36 in vivo and the activity of a high molecular weight I{kappa}B kinase complex in vitro. Subsequently, others have identified two proteins, I{kappa}B kinase (IKK-) and I{kappa}B kinase {beta} (IKK-{beta}), that are present in a tumor necrosis factor -inducible, high molecular weight I{kappa}B kinase complex. These kinases are believed to directly phosphorylate I{kappa}B based on the examination of the kinase activities of IKK immunoprecipitates, but more rigorous proof of this has yet to be demonstrated. We show herein that recombinant IKK- and IKK-{beta} can, in fact, directly phosphorylate I{kappa}B at Ser-32 and Ser-36, as well as homologous residues in I{kappa}B{beta} in vitro, and thus are bona fide I{kappa}B kinases. We also show that MEKK1 can induce the activation of both IKK- and IKK-{beta} in vivo. Finally, we show that IKK- is present in the MEKK1-inducible, high molecular weight I{kappa}B kinase complex and treatment of this complex with MEKK1 induces phosphorylation of IKK- in vitro. We conclude that IKK- and IKK-{beta} can mediate the NF-{kappa}B-inducing activity of MEKK1.
