The CARMA1/CARD11-BCL10-MALT1 (CBM) complex bridges T and B cell antigen receptor (TCR/BCR) ligation to MALT1 protease activation and canonical nuclear factor κB (NF-κB) signaling. Using unbiased mass spectrometry, we discover multiple serine phosphorylation sites in the MALT1 C terminus after T cell activation. Phospho-specific antibodies reveal that CBM-associated MALT1 is transiently hyper-phosphorylated upon TCR/CD28 co-stimulation. We identify a dual role for CK1α as a kinase that is essential for CBM signalosome assembly as well as MALT1 phosphorylation. Although MALT1 phosphorylation is largely dispensable for protease activity, it fosters canonical NF-κB signaling in Jurkat and murine CD4 T cells. Moreover, constitutive MALT1 phosphorylation promotes survival of activated B cell-type diffuse large B cell lymphoma (ABC-DLBCL) cells addicted to chronic BCR signaling. Thus, MALT1 phosphorylation triggers optimal NF-κB activation in lymphocytes and survival of lymphoma cells.

CARMA1 / CARD11-BCL10-MALT1（CBM）复合物将T细胞和B细胞抗原受体（TCR / BCR）连接桥接到MALT1蛋白酶激活和典型核因子κB（NF-κB）信号传导。使用无偏质谱技术，我们发现T细胞活化后MALT1 C末端有多个丝氨酸磷酸化位点。磷酸化特异性抗体显示，与CBM相关的MALT1在TCR / CD28共同刺激后瞬时过度磷酸化。我们确定CK1α作为激酶的双重作用，这对CBM信号体装配以及MALT1磷酸化至关重要。尽管MALT1磷酸化对于蛋白酶活性而言很大程度上是可有可无的，但它可以在Jurkat和鼠CD4 T细胞中促进经典的NF-κB信号传导。而且，组成型MALT1磷酸化促进成瘾的B细胞型弥漫性大B细胞淋巴瘤（ABC-DLBCL）细胞对慢性BCR信号的依赖而存活。因此，MALT1磷酸化可触发淋巴细胞中最佳的NF-κB活化和淋巴瘤细胞的存活。