Bcl10 controls TCR- and FcgammaR-induced actin polymerization.
Bcl10 plays an essential role in the adaptive immune response, because Bcl10-deficient lymphocytes show impaired Ag receptor-induced NF-kappaB activation and cytokine production. Bcl10 is a phosphoprotein, but the physiological relevance of this posttranslational modification remains poorly defined. In this study, we report that Bcl10 is rapidly phosphorylated upon activation of human T cells by PMA/ionomycin- or anti-CD3 treatment, and identify Ser(138) as a key residue necessary for Bcl10 phosphorylation. We also show that a phosphorylation-deficient Ser(138)/Ala mutant specifically inhibits TCR-induced actin polymerization yet does not affect NF-kappaB activation. Moreover, silencing of Bcl10, but not of caspase recruitment domain-containing MAGUK protein-1 (Carma1) induces a clear defect in TCR-induced F-actin formation, cell spreading, and conjugate formation. Remarkably, Bcl10 silencing also impairs FcgammaR-induced actin polymerization and phagocytosis in human monocytes. These results point to a key role of Bcl10 in F-actin-dependent immune responses of T cells and monocytes/macrophages.
Rueda
Daniel
D
Department of Biochemistry, University of Lausanne, BIL Biomedical Research Center, Chemin des Boveresses 155, Epalinges, Switzerland.
Gaide
Olivier
O
Ho
Liza
L
Lewkowicz
Elodie
E
Niedergang
Florence
F
Hailfinger
Stephan
S
Rebeaud
Fabien
F
Guzzardi
Montserrat
M
Conne
Béatrice
B
Thelen
Marcus
M
Delon
Jérôme
J
Ferch
Uta
U
Mak
Tak W
TW
Ruland
Jürgen
J
Schwaller
Jürg
J
Thome
Margot
M
D000199:Actins / Q000378:metabolism*; D048868:Adaptor Proteins, Signal Transducing / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology*; D000074018:B-Cell CLL-Lymphoma 10 Protein; D002478:Cells, Cultured; D006801:Humans; D008213:Lymphocyte Activation; D016328:NF-kappa B / Q000378:metabolism; D010587:Phagocytosis / Q000235:genetics; D010766:Phosphorylation; D051567:Proto-Oncogene Proteins c-vav / Q000378:metabolism; D011948:Receptors, Antigen, T-Cell / Q000276:immunology*; D017452:Receptors, IgG / Q000276:immunology*; D012694:Serine / Q000235:genetics / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology*; D020764:cdc42 GTP-Binding Protein / Q000378:metabolism; D020830:rac1 GTP-Binding Protein / Q000378:metabolism
D000199:Actins; D048868:Adaptor Proteins, Signal Transducing; D000074018:B-Cell CLL-Lymphoma 10 Protein; C118591:BCL10 protein, human; D016328:NF-kappa B; D051567:Proto-Oncogene Proteins c-vav; D011948:Receptors, Antigen, T-Cell; D017452:Receptors, IgG; D012694:Serine; D020764:cdc42 GTP-Binding Protein; D020830:rac1 GTP-Binding Protein