| First Author | Hirano M | Year | 1996 |
| Journal | J Biol Chem | Volume | 271 |
| Issue | 22 | Pages | 13234-8 |
| PubMed ID | 8662753 | Mgi Jnum | J:33239 |
| Mgi Id | MGI:80719 | Doi | 10.1074/jbc.271.22.13234 |
| Citation | Hirano M, et al. (1996) MEK kinase is involved in tumor necrosis factor alpha-induced NF-kappaB activation and degradation of IkappaB-alpha. J Biol Chem 271(22):13234-8 |
| abstractText | Signal-dependent activation of the transcription factor NF-kappaB is dominantly regulated by degradation of IkappaB-alpha protein. However, the signaling pathways that lead to the degradation are not clear. Here we report that mitogen-activated protein kinase/extracellular signal-regulated kinase kinase (MEK) kinase, an activator of stress-activated protein kinases/jun kinase-1 (SAPKs/JNK1), is involved in such signaling pathways. The transient overexpression of MEK kinase in NIH3T3 fibroblasts activates kappaB-CAT reporter expression in a synergistic manner with TNFalpha stimulation. In contrast, overexpression of kinase-negative MEK kinase suppresses TNFalpha-induced reporter expression. The overexpression of MEK kinase suppresses the inhibitory activity of co-transfected IkappaB-alpha on the kappaB-CAT or human immunodeficiency virus-long terminal repeat-luciferase reporter expression and causes the simultaneous disappearance of the overexpressed IkappaB-alpha. The disappearance of exogenous IkappaB-alpha by the overexpression of MEK kinase is prevented by calpain inhibitor-I, an inhibitor of IkappaB-alpha degradation. These results suggest that MEK kinase is a signal mediator involved in TNFalpha-induced NF-kappaB activation and that the activation of NF-kappaB by MEK kinase is regulated through the degradation of IkappaB-alpha. |
