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

Research output: Contribution to journalArticle

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Abstract

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.

Original languageEnglish (US)
Pages (from-to)43541-43549
Number of pages9
JournalJournal of Biological Chemistry
Volume278
Issue number44
DOIs
StatePublished - Oct 31 2003

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Immunological Synapses
Guanine Nucleotide Exchange Factors
T-Cell Antigen Receptor
rho GTP-Binding Proteins
T-cells
T-Lymphocytes
Antigen Receptors
Phosphorylation
Viral Tumor Antigens
Antigen-Presenting Cells
Actin Cytoskeleton
Synapses
Tyrosine
Actins
Proteins
Chemical activation
O,O-diisopropyl-S-benzylthiophosphate

ASJC Scopus subject areas

  • Biochemistry

Cite this

T Cell Receptor Engagement Leads to the Recruitment of IBP, a Novel Guanine Nucleotide Exchange Factor, to the Immunological Synapse. / Gupta, Sanjay; Fanzo, Jessica C.; Hu, Chuanmin; Cox, Dianne; Jang, So Young; Lee, Andrea E.; Greenberg, Steven; Pernis, Alessandra B.

In: Journal of Biological Chemistry, Vol. 278, No. 44, 31.10.2003, p. 43541-43549.

Research output: Contribution to journalArticle

Gupta, Sanjay ; Fanzo, Jessica C. ; Hu, Chuanmin ; Cox, Dianne ; Jang, So Young ; Lee, Andrea E. ; Greenberg, Steven ; Pernis, Alessandra B. / T Cell Receptor Engagement Leads to the Recruitment of IBP, a Novel Guanine Nucleotide Exchange Factor, to the Immunological Synapse. In: Journal of Biological Chemistry. 2003 ; Vol. 278, No. 44. pp. 43541-43549.
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