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Kutzner, K. ; Woods, S. ; Karayel, O.* ; Gehring, T. ; Yin, H. ; Flatley, A. ; Grass, C. ; Wimberger, N. ; Tofaute, M.J. ; Seeholzer, T. ; Feederle, R. ; Mann, M.* ; Krappmann, D.

Phosphorylation of serine-893 in CARD11 suppresses the formation and activity of the CARD11-BCL10-MALT1 complex in T and B cells.

Sci. Signal. 15:eabk3083 (2022)
Postprint DOI PMC
Open Access Green
CARD11 acts as a gatekeeper for adaptive immune responses after T cell or B cell antigen receptor (TCR/BCR) ligation on lymphocytes. PKCθ/β-catalyzed phosphorylation of CARD11 promotes the assembly of the CARD11-BCL10-MALT1 (CBM) complex and lymphocyte activation. Here, we demonstrated that PKCθ/β-dependent CARD11 phosphorylation also suppressed CARD11 functions in T or B cells. Through mass spectrometry-based proteomics analysis, we identified multiple constitutive and inducible CARD11 phosphorylation sites in T cells. We demonstrated that a single TCR- or BCR-inducible phosphorylation on Ser893 in the carboxyl terminus of CARD11 prevented the activation of the transcription factor NF-κB, the kinase JNK, and the protease MALT1. Moreover, CARD11 Ser893 phosphorylation sensitized BCR-addicted lymphoma cells to toxicity induced by Bruton's tyrosine kinase (BTK) inhibitors. Phosphorylation of Ser893 in CARD11 by PKCθ controlled the strength of CARD11 scaffolding by impairing the formation of the CBM complex. Thus, PKCθ simultaneously catalyzes both stimulatory and inhibitory CARD11 phosphorylation events, which shape the strength of CARD11 signaling in lymphocytes.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Korrespondenzautor
Schlagwörter Malt1 Protease; Kinase-beta; Activation; Carma1; Domain; Ubiquitination; Lymphocytes; Extraction; Mutations; Mechanism
ISSN (print) / ISBN 1945-0877
e-ISSN 1937-9145
Zeitschrift Science Signaling
Quellenangaben Band: 15, Heft: 723, Seiten: , Artikelnummer: eabk3083 Supplement: ,
Verlag American Association for the Advancement of Science (AAAS)
Verlagsort 1200 New York Ave, Nw, Washington, Dc 20005 Usa
Nichtpatentliteratur Publikationen
Begutachtungsstatus Peer reviewed
Institut(e) Research Unit Signaling and Translation (SAT)
Institute of Molecular Toxicology and Pharmacology (TOXI)
CF Monoclonal Antibodies (CF-MAB)
Förderungen Deutsche Forschungsgemeinschaft (DFG)
Deutsche Krebshilfe award