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Molecular and Cellular Biology, October 2005, p. 8486-8495, Vol. 25, No. 19
0270-7306/05/$08.00+0     doi:10.1128/MCB.25.19.8486-8495.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Cbp Deficiency Alters Csk Localization in Lipid Rafts but Does Not Affect T-Cell Development

Shengli Xu, Jianxin Huo, Joy En-Lin Tan, and Kong-Peng Lam*

Laboratory of Immunology, Centre for Molecular Medicine and Institute of Molecular and Cell Biology, Singapore, Singapore

Received 13 January 2005/ Returned for modification 12 March 2005/ Accepted 14 July 2005

The ubiquitously expressed transmembrane adaptor Csk-binding protein (Cbp) recruits Csk to lipid rafts, where the latter exerts its negative regulatory effect on the Src family of protein tyrosine kinases. We have inactivated Cbp in the mouse germ line. In contrast to Csk gene inactivation, which leads to embryonic lethality and impaired T-cell development, Cbp-deficient mice were viable and exhibited normal T-cell development but with an increased thymocyte population. In the absence of Cbp, the amount of Csk that localizes to the lipid rafts was greatly reduced. Interestingly, this altered lipid raft localization of Csk did not lead to any detectable biochemical or functional defect in T cells. The T-cell receptor-induced intracellular calcium flux, cell proliferation, and cytokine secretion were not affected by the absence of Cbp. Peripheral T-cell tolerance to superantigen SEB was also largely intact in Cbp-deficient mice. Thus, Cbp is dispensable for T-cell development and activation.

* Corresponding author. Mailing address: Laboratory of Immunology, Center for Molecular Medicine, Institute of Molecular and Cell Biology, 61 Biopolis Drive, Lab 6-15, Proteos, Singapore 138673, Singapore. Phone: 65 6586 9647. Fax: 65 6779 1117. E-mail: mcblamkp{at}imcb.a-star.edu.sg.

Molecular and Cellular Biology, October 2005, p. 8486-8495, Vol. 25, No. 19
0022-538X/05/$08.00+0     doi:10.1128/MCB.25.19.8486-8495.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.



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