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.
Yamaguchi
Tadayuki
T
Department of Biosciences, Kitasato University, Sagamihara, Kanagawa, Japan.
Miyashita
Chiaki
C
Koyano
Satoru
S
Kanda
Hiromi
H
Yoshioka
Katsuji
K
Shiba
Tadayoshi
T
Takamatsu
Nobuhiko
N
Ito
Michihiko
M
D000818:Animals; D019556:COS Cells; D002460:Cell Line; D002522:Chlorocebus aethiops; D047468:Immunoprecipitation; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism*; D020930:MAP Kinase Kinase Kinases / Q000378:metabolism*; D020935:MAP Kinase Signaling System; D051379:Mice; D016328:NF-kappa B / Q000378:metabolism*; D015398:Signal Transduction; D047992:TNF Receptor-Associated Factor 2 / Q000378:metabolism*; D014162:Transfection; D000099151:MAP Kinase Kinase Kinase 7
D047908:Intracellular Signaling Peptides and Proteins; D020930:MAP Kinase Kinase Kinases; D016328:NF-kappa B; D047992:TNF Receptor-Associated Factor 2; D000099151:MAP Kinase Kinase Kinase 7; C121624:Mapkbp1 protein, mouse