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, Alessandra B. Pernis
2003 Journal of Biological Chemistry  
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
more » ... c42 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 3,4,5trisphosphate. 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.
doi:10.1074/jbc.m308960200 pmid:12923183 fatcat:vdb2iwymsbhz7iwvfejqqk3bxq