[en] The Csk tyrosine kinase negatively regulates the Src family kinases Lek and Fyn in T cells. Engagement of the T-cell antigen receptor results in a removal of Csk from the lipid raft-associated transmembrane protein PAG/Cbp. Instead, Csk becomes associated with an similar to72-kDa tyrosine-phosphorylated protein, which we identify here as G3BP, a phosphoprotein reported to bind the SH3 domain of Ras GTPase-activating protein. G3BP reduced the ability of Csk to phosphorylate Lek at Y505 by decreasing the amount of Csk in lipid rafts. As a consequence, G3BP augmented T-cell activation as measured by interleukin-2 gene activation. Conversely, elimination of endogenous G3BP by RNA interference increased Lek Y505 phosphorylation and reduced TCR signaling. In antigen-specific T cells, endogenous G3BP moved into a intracellular location adjacent to the immune synapse, but deeper inside the cell, upon antigen recognition. Csk colocalization with G3BP occurred in this "parasynaptic" location. We conclude that G3BP is a new player in T-cell-antigen receptor signaling and acts to reduce the amount of Csk in the immune synapse.
Disciplines :
Biochemistry, biophysics & molecular biology
Author, co-author :
Rahmouni, Souad ; Université de Liège - ULiège > Département des sciences cliniques > Immunopathologie - Transplantation
Vang, Torkel; Burnham Institute > Cancer Center
Alonso, Andres; Burnham Institute > Cancer Center
Williams, Scott; Burnham Institute > Cancer Center
van Stipdonk, Marianne; La Jolla Institute for Allergy and Immunology > Division of Immune Regulation
Soncini, Chiara; Pharmacia Corporation > Discovery Research Oncology
Moutschen, Michel ; Université de Liège - ULiège > Département des sciences cliniques > Immunopathologie - Transplantation
Schoenberger, Stephen P.; La Jolla Institute for Allergy and Immunology > Division of Immune Regulation
Mustelin, Tomas; Burnham Institute > Cancer Center
Language :
English
Title :
Removal of C-terminal Src kinase from the immune synapse by a new binding protein
Publication date :
March 2005
Journal title :
Molecular and Cellular Biology
ISSN :
0270-7306
eISSN :
1098-5549
Publisher :
Amer Soc Microbiology, Washington, United States - Washington
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