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

Gehring, Torben; Erdmann, Tabea; Rahm, Marco; Gras, Carina; Flatley, Andrew; O'Neill, Thomas J.; Woods, Simone; Meininger, Isabel; Karayel, Ozge; Kutzner, Kerstin; Grau, Michael; Shinohara, Hisaaki; Lammens, Katja; Feederle, Regina; Hauck, Stefanie M.; Lenz, Georg und Krappmann, Daniel (2019): MALT1 Phosphorylation Controls Activation of T Lymphocytes and Survival of ABC-DLBCL Tumor Cells. In: Cell Reports, Bd. 29, Nr. 4

Abstract

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 kappa B (NF-kappa B) 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 CK1 alpha 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-kappa B 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-kappa B activation in lymphocytes and survival of lymphoma cells.

• Dokumententyp: Zeitschriftenartikel
• Fakultät: Chemie und Pharmazie > Department Biochemie
• Themengebiete: 500 Naturwissenschaften und Mathematik > 540 Chemie
• ISSN: 2211-1247
• Sprache: Englisch