JNK-binding protein 1 regulates NF-kappaB activation through TRAF2 and TAK1.
The mitogen-activated protein kinase (MAPK) cascades, including c-Jun N-terminal kinase (JNK), are composed of a MAPK, MAPK kinase (MAPKK), and MAPKK kinase (MAPKKK). Previously, we reported that JNK-binding protein 1 (JNKBP1) enhances JNK activation induced by the TGF-beta-activated kinase1 (TAK1) MAPKKK in transfected cells. We have investigated whether JNKBP1 functions ... as an adaptor protein for nuclear factor (NF)-kappaB activation mediated by TAK1 in COS-7 cells. Co-expression experiments showed that JNKBP1 interacted with not only TAK1, but also with its upstream regulators, TNF-receptor associated factors 2 and 6 (TRAF2 and TRAF6). An endogenous interaction between JNKBP1 and TRAF2 or TAK1 was confirmed by immunoprecipitation analysis. We also found that JNKBP1 could enhance the NF-kappaB activation induced by TAK1 and TRAF2, and could promote TRAF2 polyubiquitination. These results suggest a scaffolding role for JNKBP1 in the TRAF2-TAK1-NF-kappaB signaling pathway.
Mesh Terms:
Animals, COS Cells, Cell Line, Cercopithecus aethiops, Immunoprecipitation, Intracellular Signaling Peptides and Proteins, MAP Kinase Kinase Kinases, MAP Kinase Signaling System, Mice, NF-kappa B, Signal Transduction, TNF Receptor-Associated Factor 2, Transfection
Animals, COS Cells, Cell Line, Cercopithecus aethiops, Immunoprecipitation, Intracellular Signaling Peptides and Proteins, MAP Kinase Kinase Kinases, MAP Kinase Signaling System, Mice, NF-kappa B, Signal Transduction, TNF Receptor-Associated Factor 2, Transfection
Cell Biol. Int.
Date: Mar. 01, 2009
PubMed ID: 19385034
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