Phosphorylation of Bcl10 negatively regulates T-cell receptor-mediated NF-kappaB activation.
Bcl10 (B-cell lymphoma 10) is an adaptor protein comprised of an N-terminal caspase recruitment domain and a C-terminal serine/threonine-rich domain. Bcl10 plays a critical role in antigen receptor-mediated NF-kappaB activation and lymphocyte development and functions. Our current study has discovered that T-cell activation induced monophosphorylation and biphosphorylation of Bcl10 and has identified S138 within Bcl10 as one of the T-cell receptor-induced phosphorylation sites. Alteration of S138 to an alanine residue impaired T-cell activation-induced ubiquitination and subsequent degradation of Bcl10, ultimately resulting in prolongation of TCR-mediated NF-kappaB activation and enhancement of interleukin-2 production. Taken together, our findings demonstrate that phosphorylation of Bcl10 at S138 down-regulates Bcl10 protein levels and thus negatively regulates T-cell receptor-mediated NF-kappaB activation.
Zeng
Hu
H
The Blood Research Institute, 8727 Watertown Plank Road, Milwaukee, WI 53226, USA.
Di
Lie
L
Fu
Guoping
G
Chen
Yuhong
Y
Gao
Xiang
X
Xu
Langlai
L
Lin
Xin
X
Wen
Renren
R
D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism*; D000818:Animals; D000074018:B-Cell CLL-Lymphoma 10 Protein; D015536:Down-Regulation / Q000235:genetics*; D006801:Humans; D007376:Interleukin-2 / Q000096:biosynthesis; D019169:Jurkat Cells; D008213:Lymphocyte Activation; D051379:Mice; D008954:Models, Biological; D016328:NF-kappa B / Q000378:metabolism*; D010766:Phosphorylation; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism*; D012694:Serine / Q000378:metabolism; D025801:Ubiquitin / Q000378:metabolism
D048868:Adaptor Proteins, Signal Transducing; D000074018:B-Cell CLL-Lymphoma 10 Protein; C118591:BCL10 protein, human; C488088:Bcl10 protein, mouse; D007376:Interleukin-2; D016328:NF-kappa B; D011948:Receptors, Antigen, T-Cell; D025801:Ubiquitin; D012694:Serine