MALT1 Phosphorylation Controls Activation of T Lymphocytes and Survival of ABC-DLBCL Tumor Cells

被引：28

作者：

Gehring, Torben ^{[1
]}

Erdmann, Tabea ^{[2
]}

Rahm, Marco ^{[3
]}

Gras, Carina ^{[1
]}

Flatley, Andrew ^{[4
,5
]}

O'Neill, Thomas J. ^{[1
]}

Woods, Simone ^{[1
]}

Meininger, Isabel ^{[1
,9
]}

Karayel, Ozge ^{[6
]}

Kutzner, Kerstin ^{[1
]}

Grau, Michael ^{[2
]}

Shinohara, Hisaaki ^{[7
]}

Lammens, Katja ^{[8
]}

Feederle, Regina ^{[4
,5
]}

Hauck, Stefanie M. ^{[3
]}

Lenz, Georg ^{[2
]}

Krappmann, Daniel ^{[1
]}

机构：

[1] German Res Ctr Environm Hlth GmbH, Inst Mol Toxicol & Pharmacol, Res Unit Cellular Signal Integrat, Helmholtz Zentrum Munchen, Ingolstadter Landstr 1, D-85764 Neuherberg, Germany

[2] Univ Hosp Munster, Dept Med A, Hematol Oncol & Pneumol, D-48149 Munster, Germany

[3] German Res Ctr Environm Hlth GmbH, Res Unit Prot Sci, Helmholtz Zentrum Munchen, Ingolstadter Landstr 1, D-85764 Neuherberg, Germany

[4] German Res Ctr Environm Hlth GmbH Ingolstadter, Inst Diabet & Obes, Helmholtz Zentrum Munchen, Monoclonal Antibody Core Facil, Ingolstadter Landstr 1, D-85764 Neuherberg, Germany

[5] German Res Ctr Environm Hlth GmbH Ingolstadter, Inst Diabet & Obes, Res Grp, Ingolstadter Landstr 1, D-85764 Neuherberg, Germany

[6] Max Planck Inst Biochem, Dept Prote & Signal Transduct, Klopferspitz 18, D-82152 Planegg, Germany

[7] Sanyo Onoda City Univ, Fac Pharmaceut Sci, Lab Syst Immunol, 1-1-1 Daigakudori, Sanyo Onoda City, Yamaguchi 7560884, Japan

[8] Ludwig Maximilians Univ Munchen, Gene Ctr, Feodor Lynen Str 25, D-81377 Munich, Germany

[9] Karolinska Inst, Ctr Infect Med, Dept Med, S-17177 Stockholm, Sweden

来源：

CELL REPORTS | 2019年 / 29卷 / 04期

关键词：

NF-KAPPA-B; PARACASPASE MALT1; CASEIN KINASE; PROTEASE ACTIVITY; CARD11; MUTATIONS; CLEAVAGE; CARMA1; BCL10; ALPHA; BETA;

D O I：

10.1016/j.celrep.2019.09.040

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

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 kappa B (NF-kappa B) 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 CK1 alpha 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-kappa B 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-kappa B activation in lymphocytes and survival of lymphoma cells.

引用

页码：873 / +

页数：26

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