MALT1 Phosphorylation Controls Activation of T Lymphocytes and Survival of ABC-DLBCL Tumor Cells

• Main Authors: Torben Gehring, Tabea Erdmann, Marco Rahm, Carina Graß, Andrew Flatley, Thomas J. O’Neill, Simone Woods, Isabel Meininger, Ozge Karayel, Kerstin Kutzner, Michael Grau, Hisaaki Shinohara, Katja Lammens, Regina Feederle, Stefanie M. Hauck, Georg Lenz, Daniel Krappmann
• Format: Article
• Language: English
• Published: Elsevier 2019-10-01
• Series: Cell Reports
• Online Access: http://www.sciencedirect.com/science/article/pii/S2211124719312288

Summary: 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. : Gehring et al. identify MALT1 phosphorylation as a process that bridges antigen receptor ligation to downstream signaling pathways in T cells, promotes T lymphocyte activation, and drives survival of B cell lymphoma tumor cells. Keywords: immune response, adaptive immunity, antigen receptor signaling, T cell activation, B cell lymphomas, CBM complex, phosphorylation, NF-kappa B, MALT1, casein kinase 1 alpha