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Homeostatic interactions between MEKK3 and TAK1 involved in NF-kappaB signaling.
- Source :
-
Cellular signalling [Cell Signal] 2008 Apr; Vol. 20 (4), pp. 705-13. Date of Electronic Publication: 2008 Jan 18. - Publication Year :
- 2008
-
Abstract
- Several members of the mitogen-activated protein kinase kinase kinase (MAP3K) family including MEKK3 and TGFbeta-activating kinase (TAK1) play nonredundant roles in activation of the NF-kappaB transcription factor. However, the mechanism by which MEKK3 mediates NF-kappaB signaling is not fully understood. In this report we investigate the association of murine MEKK3 with other proteins and their roles in NF-kappaB activation. Using tandem affinity purification TAK1 was identified as an endogenous protein that interacts with MEKK3. MEKK3-TAK1 interactions were confirmed by fluorescence resonance energy transfer and coimmunoprecipitation. MEKK3-TAK1 complexes contain non-phosphorylated forms of both molecules. Expression of non-phosphorylated TAK1 interferes with MEKK3 phosphorylation and NF-kappaB reporter activity induced by transient MEKK3 expression or TNFalpha stimulation. Addition of TAB1 facilitates TAK1 autophosphorylation and reverses the inhibitory effects of TAK1 on MEKK3 phosphorylation and NF-kappaB signal transduction in human 293 cells and TAK1 deficient mouse embryonic fibroblasts. The data provide insights into the homeostatic interactions that maintain basal NF-kappaB levels by holding the enzymes MEKK3 and TAK1 in their inactive state.
- Subjects :
- Animals
Cell Line
Chromatography, Affinity
Enzyme Activation
Epithelial Cells enzymology
Epithelial Cells metabolism
Fibroblasts enzymology
Fibroblasts metabolism
Fluorescence Resonance Energy Transfer
Homeostasis
Humans
Intracellular Signaling Peptides and Proteins metabolism
MAP Kinase Kinase Kinase 3 genetics
MAP Kinase Kinase Kinases deficiency
MAP Kinase Kinase Kinases genetics
Mice
Mutation
Phosphorylation
Protein Binding
Transfection
Tumor Necrosis Factor-alpha metabolism
MAP Kinase Kinase Kinase 3 metabolism
MAP Kinase Kinase Kinases metabolism
NF-kappa B metabolism
Signal Transduction
Subjects
Details
- Language :
- English
- ISSN :
- 0898-6568
- Volume :
- 20
- Issue :
- 4
- Database :
- MEDLINE
- Journal :
- Cellular signalling
- Publication Type :
- Academic Journal
- Accession number :
- 18206350
- Full Text :
- https://doi.org/10.1016/j.cellsig.2007.12.007