NAK is an IκB kinase-activating kinase

Yulchiro Tojima, Atsushi Fujimoto, Mireille Delhase, Yi Chen, Shigetsugu Hatekeyama, Kei Ichi Nakayama, Yoko Kaneko, Yuji Nimura, Noboru Motoyama, Kyoji Ikeda, Michael Karin, Makoto Nakanishi

研究成果: ジャーナルへの寄稿記事

275 引用 (Scopus)

抄録

Phosphorylation of IκB by the IκB kinase (IKK) complex is a critical step leading to IκB degradation and activation of transcription factor NF- κB. The IKK complex contains two catalytic subunits, IKKα and IKKβ, the latter being indispensable for NFKB activation by pro-inflammatory cytokines. Although IKK is activated by phosphorylation of the IKKβ activation loop, the physiological IKK kinases that mediate responses to extracellular stimuli remain obscure. Here we describe an IKK-related kinase, named NAK (NF-κB- activating kinase), that can activate IKK through direct phosphorylation. NAK induces IκB degradation and NF-κB activity through IKKβ. Endogenous NAK is activated by phorbol ester tumour promoters and growth factors, whereas catalytically inactive NAK specifically inhibits activation of NFKB by protein kinase C-ε (PKCε). Thus, NAK is an IKK kinase that may mediate IKK and NF-κB activation in response to growth factors that stimulate PKCε activity.

元の言語英語
ページ(範囲)778-782
ページ数5
ジャーナルNature
404
発行部数6779
DOI
出版物ステータス出版済み - 4 13 2000

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Phosphotransferases
Phosphorylation
Protein Kinase C
Intercellular Signaling Peptides and Proteins
Phorbol Esters
Carcinogens
Catalytic Domain
Transcription Factors
Cytokines

All Science Journal Classification (ASJC) codes

  • General

これを引用

Tojima, Y., Fujimoto, A., Delhase, M., Chen, Y., Hatekeyama, S., Nakayama, K. I., ... Nakanishi, M. (2000). NAK is an IκB kinase-activating kinase. Nature, 404(6779), 778-782. https://doi.org/10.1038/35008109

NAK is an IκB kinase-activating kinase. / Tojima, Yulchiro; Fujimoto, Atsushi; Delhase, Mireille; Chen, Yi; Hatekeyama, Shigetsugu; Nakayama, Kei Ichi; Kaneko, Yoko; Nimura, Yuji; Motoyama, Noboru; Ikeda, Kyoji; Karin, Michael; Nakanishi, Makoto.

:: Nature, 巻 404, 番号 6779, 13.04.2000, p. 778-782.

研究成果: ジャーナルへの寄稿記事

Tojima, Y, Fujimoto, A, Delhase, M, Chen, Y, Hatekeyama, S, Nakayama, KI, Kaneko, Y, Nimura, Y, Motoyama, N, Ikeda, K, Karin, M & Nakanishi, M 2000, 'NAK is an IκB kinase-activating kinase', Nature, 巻. 404, 番号 6779, pp. 778-782. https://doi.org/10.1038/35008109
Tojima Y, Fujimoto A, Delhase M, Chen Y, Hatekeyama S, Nakayama KI その他. NAK is an IκB kinase-activating kinase. Nature. 2000 4 13;404(6779):778-782. https://doi.org/10.1038/35008109
Tojima, Yulchiro ; Fujimoto, Atsushi ; Delhase, Mireille ; Chen, Yi ; Hatekeyama, Shigetsugu ; Nakayama, Kei Ichi ; Kaneko, Yoko ; Nimura, Yuji ; Motoyama, Noboru ; Ikeda, Kyoji ; Karin, Michael ; Nakanishi, Makoto. / NAK is an IκB kinase-activating kinase. :: Nature. 2000 ; 巻 404, 番号 6779. pp. 778-782.
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AU - Nakayama, Kei Ichi

AU - Kaneko, Yoko

AU - Nimura, Yuji

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AB - Phosphorylation of IκB by the IκB kinase (IKK) complex is a critical step leading to IκB degradation and activation of transcription factor NF- κB. The IKK complex contains two catalytic subunits, IKKα and IKKβ, the latter being indispensable for NFKB activation by pro-inflammatory cytokines. Although IKK is activated by phosphorylation of the IKKβ activation loop, the physiological IKK kinases that mediate responses to extracellular stimuli remain obscure. Here we describe an IKK-related kinase, named NAK (NF-κB- activating kinase), that can activate IKK through direct phosphorylation. NAK induces IκB degradation and NF-κB activity through IKKβ. Endogenous NAK is activated by phorbol ester tumour promoters and growth factors, whereas catalytically inactive NAK specifically inhibits activation of NFKB by protein kinase C-ε (PKCε). Thus, NAK is an IKK kinase that may mediate IKK and NF-κB activation in response to growth factors that stimulate PKCε activity.

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