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J. Biol. Chem., Vol. 278, Issue 44, 43541-43549, October 31, 2003

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T Cell Receptor Engagement Leads to the Recruitment of IBP, a Novel Guanine Nucleotide Exchange Factor, to the Immunological Synapse^*

Sanjay Gupta, Jessica C. Fanzo, Chuanmin Hu**, Dianne Cox, So Young Jang, Andrea E. Lee, Steven Greenberg¶, and Alessandra B. Pernis||

From the Departments of Medicine and ^¶Medicine and Pharmacology, Columbia University, New York, New York 10032 and Departments of Anatomy and Structural Biology and Developmental and Molecular Biology, Albert Einstein College of Medicine, Bronx, NY 10461

Reorganization of the actin cytoskeleton is crucial to the formation and function of the immunological synapse. Rho GTPases are critical mediators of cytoskeletal reorganization, and their activity at the synapse is likely to be stringently regulated. Guanine nucleotide exchange factors (GEFs) belonging to the Dbl family of proteins represent one major class of proteins that regulate the activity of Rho GTPases. Here we demonstrate that IBP, a homologue of SWAP-70, is a novel GEF for Rac1 and Cdc42 in T lymphocytes, which is recruited to the immunological synapse upon engagement of the antigen receptor. Mutational analysis supports a model whereby IBP is inactive in unstimulated cells. Upon engagement of the T cell receptor, its GEF activity is enhanced by tyrosine phosphorylation, as well as by binding newly generated phosphatidylinositol 3,4,5-trisphosphate. Although it is known that T cell receptor engagement leads to the recruitment of Vav to the immunological synapse, these findings indicate that other GEFs, such as IBP, also relocalize to this intercellular region. The recruitment and activation of distinct classes of GEFs may allow for precise control of Rho GTPase function at the crucial interface between T cells and antigen presenting cells.

Received for publication, August 13, 2003

^* This work was supported in part by National Institutes of Health Grants R01 HL-62215 and PO1 AI50514-01 (to A. B. P.) and by a Stephen I. Morse Fellowship (to J. C. F.). 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.

^** Present address: Dept. of Clinical Biochemistry, Third Military Medical University, Chongqing 400038, People's Republic of China.

^|| To whom correspondence should be addressed: Dept. of Medicine, Columbia University, 630 West 168th St., New York, NY 10032. Tel.: 212-305-3763; Fax: 212-305-4478; E-mail: abp1{at}columbia.edu.

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