Directional Phosphorylation Leads to NF-{kappa}B Activation

doi:10.1126/stke.2000.19.tw5

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Sci. STKE, 15 February 2000
Vol. 2000, Issue 19, p. tw5
[DOI: 10.1126/stke.2000.19.tw5]

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TRANSCRIPTIONAL REGULATION Directional Phosphorylation Leads to NF- ${kappa}$ B Activation

Abstract: The inactive transcription factor NF- ${kappa}$ B is sequestered in thecytoplasmic compartment through association with the inhibitorymolecule I ${kappa}$ B. I ${kappa}$ B kinases (IKK) phosphorylate I ${kappa}$ B whereby NF- ${kappa}$ Bis released and translocates to the nucleus to induce specificgene expression. IKK ${kappa}$ and IKKß are critical for the properregulation of NF- ${kappa}$ B activity; however, there are conflictingreports on their specific roles. O'Mahony et al. demonstratedthat the presence of IKK ${alpha}$ in heterodimers with IKKß inhibitsthe high basal activity of IKKß. Signal-activated IKK ${alpha}$ phosphorylated and activated IKKß leading to the derepressionof NF- ${kappa}$ B. This chain of phosphorylation was unidirectional, asIKKß did not phosphorylate IKK ${alpha}$ under the conditions used.The MAP kinase kinase kinase Cot/Tpl-2 also phosphorylated catalyticallyinactive IKKß in the absence of IKK ${alpha}$ ; however, the physiologicalrelevance of this observation is unclear.

O'Mahony, A., Lin, X., Geleziunas, R., and Greene, W.C. (2000)Activation of the heterodimeric I ${kappa}$ B kinase ${alpha}$ (IKK ${alpha}$ )-IKKßcomplex is directional: IKK ${alpha}$ regulates IKKß under bothbasal and stimulated conditions. Mol. Cell. Biol. 20: 1170-1178. [Abstract] [Full Text]