Role of IB kinase in regulating the remodeling of the CARMA1-Bcl10-MALT1 complex.
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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-B activation upon platelet stimulation, the signals that elicit its formation and downstream effector activation remain elusive. We demonstrate herein that IKK 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 IKK regulates these processes via modulation of phosphorylation of Bcl10 and IKK polyubiquitination. Collectively, our data demonstrate that IKK regulates membrane fusion and the remodeling of the CBM complex formation.