MALT1 Phosphorylation Controls Activation of T Lymphocytes and Survival of ABC-DLBCL Tumor Cells
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説明
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 κB (NF-κB) 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 CK1α 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-κB 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-κB activation in lymphocytes and survival of lymphoma cells.
収録刊行物
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- Cell Reports
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Cell Reports 29 873-888.e10, 2019-10-01
Elsevier BV
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キーワード
- QH301-705.5
- T-Lymphocytes
- Amino Acid Motifs
- Lymphocyte Activation
- Jurkat Cells
- Mice
- CD28 Antigens
- Animals
- Humans
- Biology (General)
- Phosphorylation
- Cells, Cultured
- 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
- Casein Kinase Ialpha
- B-Cell CLL-Lymphoma 10 Protein
- CARD Signaling Adaptor Proteins
- Mice, Inbred C57BL
- HEK293 Cells
- Guanylate Cyclase
- Mucosa-Associated Lymphoid Tissue Lymphoma Translocation 1 Protein
- Lymphoma, Large B-Cell, Diffuse
- Signal Transduction
