Positive feedback within a kinase signaling complex functions as a switch mechanism for NF-κB activation

Hisaaki Shinohara, Marcelo Behar, Kentaro Inoue, Michio Hiroshima, Tomoharu Yasuda, Takeshi Nagashima, Shuhei Kimura, Hideki Sanjo, Shiori Maeda, Noriko Yumoto, Sewon Ki, Shizuo Akira, Yasushi Sako, Alexander Hoffmann, Tomohiro Kurosaki, Mariko Okada-Hatakeyama

研究成果: ジャーナルへの寄稿学術誌査読

67 被引用数 (Scopus)

抄録

A switchlike response in nuclear factor-κB (NF-κB) activity implies the existence of a threshold in the NF-κB signaling module. We show that the CARD-containing MAGUK protein 1 (CARMA1, also called CARD11)-TAK1 (MAP3K7)-inhibitor of NF-κB (IκB) kinase-b (IKKβ) module is a switch mechanism for NF-κB activation in B cell receptor (BCR) signaling. Experimental and mathematical modeling analyses showed that IKK activity is regulated by positive feedback from IKKβ to TAK1, generating a steep dose response to BCR stimulation. Mutation of the scaffolding protein CARMA1 at serine-578, an IKKβ target, abrogated not only late TAK1 activity, but also the switchlike activation of NF-κB in single cells, suggesting that phosphorylation of this residue accounts for the feedback.

本文言語英語
ページ(範囲)760-764
ページ数5
ジャーナルScience
344
6185
DOI
出版ステータス出版済み - 2014
外部発表はい

!!!All Science Journal Classification (ASJC) codes

  • 一般

フィンガープリント

「Positive feedback within a kinase signaling complex functions as a switch mechanism for NF-κB activation」の研究トピックを掘り下げます。これらがまとまってユニークなフィンガープリントを構成します。

引用スタイル