Journal Club

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

Science Signaling 1 Mar 2022 • Vol 15, Issue 723

Putting the brakes on lymphocyte activation

Stimulation of antigen receptors on T or B cells leads to the formation of a complex consisting of the scaffolding protein CARD11, the linking factor BCL10, and the protease MALT1 (CBM), which ultimately results in T or B cell activation. The ability of CARD11 to recruit BCL10 and MALT1 is regulated by multiple phosphorylation events mediated by various kinases. Using biochemical techniques and T and B cell lines expressing phosphorylation mutants of CARD11, Kutzner et al. identified Ser893 as an inhibitory phosphorylation site that restrained antigen receptor–induced CBM formation and lymphocyte activation. This phosphorylation event prevented the activation of T cells without coreceptor stimulation and sensitized B cell lymphomas to inhibitors used to treat this cancer type. Because PKCθ also mediates stimulatory phosphorylation events for CARD11, the authors speculate that the combination of stimulatory and inhibitory phosphorylation events sets signaling thresholds for lymphocyte activation.