IKK beta plays an essential role in the phosphorylation of RelA/p65 on serine 536 induced by lipopolysaccharide.
Activation of the I kappa B kinase (IKK) complex by LPS induces phosphorylation and degradation of I kappa B alpha, leading to the nuclear translocation of NF-kappa B. Although it is essential for NF-kappa B activation, emerging evidence has indicated that the nuclear translocation of NF-kappa B is not sufficient to activate NF-kappa B-dependent transcription. Here, we reported that LPS induced the phosphorylation of the p65 trans-activation domain on serine 536 in monocytes/macrophages. Using mouse embryonic fibroblasts lacking either IKK alpha or IKK beta, we found that IKK beta played an essential role in LPS-induced p65 phosphorylation on serine 536, while IKK alpha was partially required for the p65 phosphorylation. The LPS-induced p65 phosphorylation on serine 536 was independent of the phosphatidylinositol 3'-kinase/Akt signaling pathway. Furthermore, we found that the phosphorylation on serine 536 increased the p65 transcription activity. In summary, our results demonstrate that IKK beta plays an essential role in the LPS-induced p65 phosphorylation on serine 536, which may represent a mechanism to regulate the NF-kappa B transcription activity by LPS.
Yang
Fan
F
Laboratory of Molecular Signaling and Apoptosis, Department of Biologic and Materials Sciences, University of Michigan, Ann Arbor, MI 48109, USA.
Tang
Eric
E
Guan
Kunliang
K
Wang
Cun-Yu
CY
D019943:Amino Acid Substitution / Q000235:genetics; D000818:Animals; D002460:Cell Line; D006801:Humans; D051550:I-kappa B Kinase; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008264:Macrophages / Q000201:enzymology / Q000276:immunology / Q000378:metabolism; D051379:Mice; D009000:Monocytes / Q000201:enzymology / Q000276:immunology / Q000378:metabolism; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D019869:Phosphatidylinositol 3-Kinases / Q000502:physiology; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D017434:Protein Structure, Tertiary / Q000235:genetics; D011518:Proto-Oncogene Proteins / Q000502:physiology; D051057:Proto-Oncogene Proteins c-akt; D012694:Serine / Q000378:metabolism*; D015398:Signal Transduction / Q000276:immunology; D051996:Transcription Factor RelA; D014158:Transcription, Genetic / Q000276:immunology; D015533:Transcriptional Activation / Q000276:immunology; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D051550:I-kappa B Kinase; D008070:Lipopolysaccharides; D016328:NF-kappa B; D019869:Phosphatidylinositol 3-Kinases; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins; D051057:Proto-Oncogene Proteins c-akt; D012694:Serine; D051996:Transcription Factor RelA; D014409:Tumor Necrosis Factor-alpha; C494918:AKT1 protein, human; C496559:CHUK protein, human; C496564:Chuk protein, mouse; C496560:IKBKB protein, human; C496565:IKBKE protein, human; C496562:Ikbkb protein, mouse; C496566:Ikbke protein, mouse