1101 N. Campbell St, Pharmaceutical Sciences, School of Pharmacy, The University of Texas El Paso, El Paso, TX 79902, USA.
The University of Texas at San Antonio, San Antonio, TX 78249, USA.
Biochem Biophys Res Commun. 2018 Jun 2;500(2):268-274. doi: 10.1016/j.bbrc.2018.04.057. Epub 2018 Apr 14.
The current work investigates the notion that inducible clustering of signaling mediators of the IKK pathway is important for platelet activation. Thus, while the CARMA1, Bcl10, and MALT1 (CBM) complex is essential for triggering IKK/NF-κB activation upon platelet stimulation, the signals that elicit its formation and downstream effector activation remain elusive. We demonstrate herein that IKKβ is involved in membrane fusion, and serves as a critical protein kinase required for initial formation and the regulation of the CARMA1/MALT1/Bcl10/CBM complex in platelets. We also show that IKKβ regulates these processes via modulation of phosphorylation of Bcl10 and IKKγ polyubiquitination. Collectively, our data demonstrate that IKKβ regulates membrane fusion and the remodeling of the CBM complex formation.
目前的工作研究了这样一种观点，即 IKK 途径的信号转导介质的诱导聚集对于血小板激活很重要。因此，虽然 CARMA1、Bcl10 和 MALT1（CBM）复合物对于血小板刺激时触发 IKK/NF-κB 激活是必不可少的，但引发其形成和下游效应子激活的信号仍然难以捉摸。我们在此证明 IKKβ 参与膜融合，并作为关键的蛋白激酶，对于初始形成和血小板中 CARMA1/MALT1/Bcl10/CBM 复合物的调节是必需的。我们还表明，IKKβ 通过调节 Bcl10 和 IKKγ 的多泛素化的磷酸化来调节这些过程。总的来说，我们的数据表明 IKKβ 调节膜融合和 CBM 复合物形成的重塑。
