1. MALT1 phosphorylation controls activation of T lymphocytes and survival of ABC-DLBCL tumor cells
- Author
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Stefanie M. Hauck, Thomas J. O’Neill, Tabea Erdmann, Michael Grau, Hisaaki Shinohara, Kerstin Kutzner, Torben Gehring, Marco Rahm, Regina Feederle, Andrew Flatley, Carina Graß, Isabel Meininger, Katja Lammens, Simone Woods, Ozge Karayel, Georg Lenz, and Daniel Krappmann
- Subjects
0301 basic medicine ,T-Lymphocytes ,Amino Acid Motifs ,Lymphocyte Activation ,Jurkat cells ,General Biochemistry, Genetics and Molecular Biology ,Serine ,03 medical and health sciences ,Jurkat Cells ,Mice ,0302 clinical medicine ,CD28 Antigens ,medicine ,Animals ,Humans ,Phosphorylation ,lcsh:QH301-705.5 ,Cells, Cultured ,Adaptive Immunity ,Antigen Receptor Signaling ,B Cell Lymphomas ,Casein Kinase 1 Alpha ,Cbm Complex ,Immune Response ,Malt1 ,Nf-kappa B ,T Cell Activation ,Chemistry ,T-cell receptor ,breakpoint cluster region ,NF-kappa B ,CD28 ,Casein Kinase Ialpha ,medicine.disease ,B-Cell CLL-Lymphoma 10 Protein ,Cell biology ,CARD Signaling Adaptor Proteins ,Mice, Inbred C57BL ,MALT1 ,030104 developmental biology ,HEK293 Cells ,lcsh:Biology (General) ,Guanylate Cyclase ,Mucosa-Associated Lymphoid Tissue Lymphoma Translocation 1 Protein ,Lymphoma, Large B-Cell, Diffuse ,Diffuse large B-cell lymphoma ,030217 neurology & neurosurgery ,Signal Transduction - Abstract
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
- Published
- 2019