PuSH - Publication Server of Helmholtz Zentrum München: Phosphorylation of serine-893 in CARD11 suppresses the formation and activity of the CARD11-BCL10-MALT1 complex in T and B cells.

Navigation

Home

Deutsch

Research

Advanced Search

Browse by ...

... Journal

... Publication Type

... Research Data

... Publication Year

Publication overview

Support & Contact

Contact persons

Help

Data protection

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

Abstract
Metrics
Extra information

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.

Altmetric

Additional Metrics?

[➜Log in]

Edit extra informations Login

Publication type Article: Journal article

Document type Scientific Article

Corresponding Author

Keywords Malt1 Protease; Kinase-beta; Activation; Carma1; Domain; Ubiquitination; Lymphocytes; Extraction; Mutations; Mechanism

ISSN (print) / ISBN 1945-0877

e-ISSN 1937-9145

Journal Science Signaling

Quellenangaben Volume: 15, Issue: 723, Article Number: eabk3083

Publisher American Association for the Advancement of Science (AAAS)

Publishing Place 1200 New York Ave, Nw, Washington, Dc 20005 Usa

Non-patent literature Publications

Reviewing status Peer reviewed

Institute(s) Research Unit Signaling and Translation (SAT)
Institute of Molecular Toxicology and Pharmacology (TOXI)
CF Monoclonal Antibodies (CF-MAB)

Grants Deutsche Forschungsgemeinschaft (DFG)
Deutsche Krebshilfe award