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Molecular and Cellular Biology, July 2007, p. 5235-5245, Vol. 27, No. 14
0270-7306/07/$08.00+0     doi:10.1128/MCB.01645-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

Phosphorylation of Bcl10 Negatively Regulates T-Cell Receptor-Mediated NF-{kappa}B Activation{triangledown}

Hu Zeng,1,2,{dagger} Lie Di,1,3,{dagger} Guoping Fu,1 Yuhong Chen,1 Xiang Gao,2 Langlai Xu,3 Xin Lin,4 and Renren Wen1*

The Blood Research Institute, Blood Center of Wisconsin, Milwaukee, Wisconsin 53226,1 Model Animal Research Center, Nanjing University, Nanjing, People's Republic of China,2 College of Life Science, Nanjing Agricultural University, Nanjing, People's Republic of China,3 Department of Molecular and Cellular Oncology, University of Texas, M. D. Anderson Cancer Center, Houston, Texas 770304

Received 3 September 2006/ Returned for modification 28 September 2006/ Accepted 7 April 2007

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-{kappa}B 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-{kappa}B 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-{kappa}B activation.


* Corresponding author. Mailing address: The Blood Research Institute, 8727 Watertown Plank Road, Milwaukee, WI 53226. Phone: (414) 937-3852. Fax: (414) 937-6284. E-mail: renren.wen{at}bcw.edu

{triangledown} Published ahead of print on 14 May 2007.

{dagger} These authors contributed equally to this work.


Molecular and Cellular Biology, July 2007, p. 5235-5245, Vol. 27, No. 14
0270-7306/07/$08.00+0     doi:10.1128/MCB.01645-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.




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