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J. Biol. Chem., Vol. 282, Issue 32, 23737-23744, August 10, 2007

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The Calponin Homology Domain of Vav1 Associates with Calmodulin and Is Prerequisite to T Cell Antigen Receptor-induced Calcium Release in Jurkat T Lymphocytes^*

Zhuo Zhou, Jie Yin, Zhixun Dou, Jun Tang, Cuizhu Zhang, and Youjia Cao¹

From the Department of Biochemistry and Molecular Biology, Key Laboratory of Bioactive Materials of Ministry of Education, College of Life Sciences, Nankai University, Tianjin 300071, China

Vav1 is a guanine nucleotide exchange factor that is expressed specifically in hematopoietic cells and plays important roles in T cell development and activation. Vav1 consists of multiple structural domains so as to facilitate both its guanine nucleotide exchange activity and scaffold function following T cell antigen receptor (TCR) engagement. Previous studies demonstrated that the calponin homology (CH) domain of Vav1 is required for TCR-stimulated calcium mobilization and thus downstream activation of nuclear factor of activated T cells. However, it remained obscure how Vav1 functions in regulating calcium flux. In an effort to explore molecules interacting with Vav1, we found that calmodulin bound to Vav1 in a calcium-dependent and TCR activation-independent manner. The binding site was mapped to the CH domain of Vav1. Reconstitution of vav1-null Jurkat T cells (J.Vav1) with CH-deleted Vav1 exhibited a severe deficiency in calcium release to the same extent as that of Jurkat cells treated with the calmodulin inhibitor or J.Vav1 cells. The defect persisted even when phospholipase-C1 was fully activated, indicating a prerequisite role of Vav1 CH domain in calcium signaling. The results suggest that Vav1 and calmodulin function cooperatively to potentiate TCR-induced calcium release. This study unveiled a mechanism by which the Vav1 CH domain is involved in calcium signaling and provides insight into our understanding of the role of Vav1 in T cell activation.

Received for publication, April 9, 2007 , and in revised form, May 29, 2007.

^* This work was supported by Natural Science Foundation of China Grant 30270308, the Ministry of Science and Technology of China Grants 2006CB910103 and 2006DFB32420, Tianjin Natural Science Foundation Grant 05YFJZJC01301, and New Century Excellent Talents Program (NCET). The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement"in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ To whom correspondence should be addressed: College of Life Sciences, Nankai University, 94 Weijin Rd., Tianjin 300071, China. Tel./Fax: 86-22-23500808; E-mail: caoyj{at}nankai.edu.cn.

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