title: Inhibition of TAK1 by kamebakaurin in dendritic cells.
abstract: Kamebakaurin (KA) has anti-cancer and anti-inflammatory activities through direct inhibition of DNA-binding activity of nuclear factor-kappa B (NF-κB) p50. We suggest here another molecular target of KA by the use of lipopolysaccharide-treated dendritic cells. In cell- and enzyme-based assays, KA directly inhibited autophosphorylation and kinase activity of TAK1, followed by the inhibition of TAK1-downstream signaling cascades, such as IKK phosphorylation-IκBα degradation-nuclear translocation of NF-κB, phosphorylation of MEK3/6-p38 mitogen activated protein kinase (MAPK), and MKK4/7-c-Jun N-terminal kinase MAPK. These results demonstrated that TAK1 might be the direct molecular target of KA.
authors.affiliation: College of Pharmacy, Chungbuk National University, Cheongju, Chungbuk, South Korea.
authors.forename: Jee Youn
authors.initials: JY
authors.lastname: Kim
authors.forename: Hyung Sook
authors.initials: HS
authors.lastname: Kim
authors.forename: Yeon Jin
authors.initials: YJ
authors.lastname: Kim
authors.forename: Hong Kyung
authors.initials: HK
authors.lastname: Lee
authors.forename: Ji Sung
authors.initials: JS
authors.lastname: Kim
authors.forename: Jong Soon
authors.initials: JS
authors.lastname: Kang
authors.forename: Jin Tae
authors.initials: JT
authors.lastname: Hong
authors.forename: Youngsoo
authors.initials: Y
authors.lastname: Kim
authors.forename: Bang Yeon
authors.initials: BY
authors.lastname: Hwang
authors.forename: Sang-Bae
authors.initials: SB
authors.lastname: Han
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D016207:Cytokines / Q000378:metabolism; D003713:Dendritic Cells / Q000187:drug effects* / Q000378:metabolism; D004224:Diterpenes / Q000494:pharmacology*; D005260:Female; D020930:MAP Kinase Kinase Kinases / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors; D016328:NF-kappa B / Q000037:antagonists & inhibitors; D009569:Nitric Oxide / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D000099151:MAP Kinase Kinase Kinase 7
chemical_list: D000893:Anti-Inflammatory Agents; D016207:Cytokines; D004224:Diterpenes; D020930:MAP Kinase Kinase Kinases; D020928:Mitogen-Activated Protein Kinases; D016328:NF-kappa B; D009569:Nitric Oxide; D011993:Recombinant Fusion Proteins; D000099151:MAP Kinase Kinase Kinase 7; C047382:kamebakaurin