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Gehring, T. ; Erdmann, T.* ; Rahm, M. ; Grass, C. ; Flatley, A. ; O´Neill, T.J. ; Woods, S. ; Meininger, I. ; Karayel, O.* ; Kutzner, K. ; Grau, M.* ; Shinohara, H.* ; Lammens, K.* ; Feederle, R. ; Hauck, S.M. ; Lenz, G.* ; Krappmann, D.

MALT1 phosphorylation controls activation of T lymphocytes and survival of ABC-DLBCL tumor cells.

Cell Rep. 29, 873-888.e10 (2019)
Publ. Version/Full Text Research data DOI PMC
Open Access Gold
Creative Commons Lizenzvertrag
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.
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Publication type Article: Journal article
Document type Scientific Article
Keywords Adaptive Immunity ; Antigen Receptor Signaling ; B Cell Lymphomas ; Casein Kinase 1 Alpha ; Cbm Complex ; Immune Response ; Malt1 ; Nf-kappa B ; Phosphorylation ; T Cell Activation; Nf-kappa-b; Paracaspase Malt1; Casein Kinase; Protease Activity; Card11 Mutations; Cleavage; Carma1; Bcl10; Alpha; Beta
Language
Publication Year 2019
HGF-reported in Year 2019
ISSN (print) / ISBN 2211-1247
e-ISSN 2211-1247
Journal Cell Reports
Quellenangaben Volume: 29, Issue: 4, Pages: 873-888.e10 Article Number: , Supplement: ,
Publisher Cell Press
Publishing Place 50 Hampshire St, Floor 5, Cambridge, Ma 02139 Usa
Reviewing status Peer reviewed
Institute(s) Research Unit Signaling and Translation (SAT)
CF Metabolomics & Proteomics (CF-MPC)
CF Monoclonal Antibodies (CF-MAB)
POF-Topic(s) 30203 - Molecular Targets and Therapies
30504 - Mechanisms of Genetic and Environmental Influences on Health and Disease
30201 - Metabolic Health
Research field(s) Enabling and Novel Technologies

Immune Response and Infection
Helmholtz Diabetes Center
PSP Element(s) G-509800-002
A-630700-001
G-505700-001
G-501760-001
G-502210-001
DOI 10.1016/j.celrep.2019.09.040
WOS ID WOS:000491881400008
Scopus ID 85073542975
PubMed ID 31644910
Erfassungsdatum 2019-10-29
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