English
 
Help Privacy Policy Disclaimer
  Advanced SearchBrowse

Item

ITEM ACTIONSEXPORT
Add to Basket
  Local TagsRelease HistoryDetailsSummary

Released
Journal Article

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

MPS-Authors
/persons/resource/persons213408

Karayel,  Ozge
Mann, Matthias / Proteomics and Signal Transduction, Max Planck Institute of Biochemistry, Max Planck Society;

/persons/resource/persons78356

Mann,  Matthias
Mann, Matthias / Proteomics and Signal Transduction, Max Planck Institute of Biochemistry, Max Planck Society;

External Resource
No external resources are shared
Fulltext (restricted access)
There are currently no full texts shared for your IP range.
Fulltext (public)

scisignal.abk3083.pdf
(Publisher version), 851KB

Supplementary Material (public)
There is no public supplementary material available
Citation

Kutzner, K., Woods, S., Karayel, O., Gehring, T., Yin, H., Flatley, A., et al. (2022). Phosphorylation of serine-893 in CARD11 suppresses the formation and activity of the CARD11-BCL10-MALT1 complex in T and B cells. Science Signaling, 15(723): eabk3083. doi:10.1126/scisignal.abk3083.


Cite as: https://hdl.handle.net/21.11116/0000-000A-1FEC-B
Abstract
CARD 11 acts as a gatekeeper for adaptive immune responses after T cell or B cell antigen receptor (TCR/BCR) ligation on lymphocytes. PKC theta/beta-catalyzed phosphorylation of CARD11 promotes the assembly of the CARD11-BCL10-MALT1 (CBM) complex and lymphocyte activation. Here, we demonstrated that PKC theta/beta-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 Ser 893 in the carboxyl terminus of CARD1 1 prevented the activation of the transcription factor NF-kappa B, the kinase JNK, and the protease MALT1. Moreover, CARD11 Ser(893) phosphorylation sensitized BCR-addicted lymphoma cells to toxicity induced by Bruton's tyrosine kinase (BTK) inhibitors. Phosphorylation of Ser 893 in CARD11 by PKCO controlled the strength of CARD11 scaffolding by impairing the formation of the CBM complex. Thus, PKCO simultaneously catalyzes both stimulatory and inhibitory CARD11 phosphorylation events, which shape the strength of CARD11 signaling in lymphocytes.