Bcl10 controls TCR- and FcgammaR-induced actin polymerization.
Details
Serval ID
serval:BIB_AE9B7825A856
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Bcl10 controls TCR- and FcgammaR-induced actin polymerization.
Journal
Journal of Immunology
ISSN
0022-1767[print], 0022-1767[linking]
Publication state
Published
Issued date
2007
Volume
178
Number
7
Pages
4373-4384
Language
english
Abstract
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.
Keywords
Actins/metabolism, Adaptor Proteins, Signal Transducing/antagonists &, inhibitors, Adaptor Proteins, Signal Transducing/genetics, Cells, Cultured, Humans, Lymphocyte Activation, NF-kappa B/metabolism, Phagocytosis/genetics, Phosphorylation, Proto-Oncogene Proteins c-vav/metabolism, Receptors, Antigen, T-Cell/immunology, Receptors, IgG/immunology, Serine/genetics, Serine/metabolism, T-Lymphocytes/immunology, cdc42 GTP-Binding Protein/metabolism, rac1 GTP-Binding Protein/metabolism
Pubmed
Web of science
Create date
24/01/2008 15:11
Last modification date
20/08/2019 15:18