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| Content Provider | PubMed Central |
|---|---|
| Author | Meyer, April N. Drafahl, Kristine A. Mcandrew, Christopher W. Gilda, Jennifer E. Gallo, Leandro H. Haas, Martin Brill, Laurence M. Donoghue, Daniel J. |
| Editor | Templeton, Dennis j. |
| Copyright Year | 2013 |
| Abstract | Signaling regulated by NFκB and related transcription factors is centrally important to many inflammatory and autoimmune diseases, cancer, and stress responses. The kinase that directly regulates the canonical NFκB transcriptional pathway, Inhibitor of κB kinase β (IKKβ), undergoes activation by Ser phosphorylation mediated by NIK or TAK1 in response to inflammatory signals. Using titanium dioxide-based phosphopeptide enrichment (TiO2)-liquid chromatography (LC)-high mass accuracy tandem mass spectrometry (MS/MS), we analyzed IKKβ phosphorylation in human HEK293 cells expressing IKKβ and FGFR2, a Receptor tyrosine kinase (RTK) essential for embryonic differentiation and dysregulated in several cancers. We attained unusually high coverage of IKKβ, identifying an abundant site of Tyr phosphorylation at Tyr169 within the Activation Loop. The phosphomimic at this site confers a level of kinase activation and NFκB nuclear localization exceeding the iconic mutant S177E/S181E, demonstrating that RTK-mediated Tyr phosphorylation of IKKβ has the potential to directly regulate NFκB transcriptional activation. |
| Related Links | http://dx.doi.org/10.1371/journal.pone.0084497 |
| Starting Page | 84497 |
| File Format | |
| ISSN | 19326203 |
| e-ISSN | 19326203 |
| Journal | PLoS ONE |
| Issue Number | 12 |
| Volume Number | 8 |
| Language | English |
| Publisher | Public Library of Science |
| Publisher Date | 2013-12-01 |
| Access Restriction | Open |
| Rights Holder | Public Library of Science |
| Subject Keyword | Biochemistry, Genetics and Molecular Biology(all) Agricultural and Biological Sciences(all) Medicine(all) Research in Higher Education |
| Content Type | Text |
| Resource Type | Article |
| Subject | Multidisciplinary |
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