Abstract:
:The Csk tyrosine kinase negatively regulates the Src family kinases Lck 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 approximately 72-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 Lck 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 Lck 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.
journal_name
Mol Cell Bioljournal_title
Molecular and cellular biologyauthors
Rahmouni S,Vang T,Alonso A,Williams S,van Stipdonk M,Soncini C,Moutschen M,Schoenberger SP,Mustelin Tdoi
10.1128/MCB.25.6.2227-2241.2005subject
Has Abstractpub_date
2005-03-01 00:00:00pages
2227-41issue
6eissn
0270-7306issn
1098-5549pii
25/6/2227journal_volume
25pub_type
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