The effects of membrane compartmentalization of csk on TCR signaling

0358089 - ÚMG 2011 RIV NL eng J - Journal Article
Otáhal, Pavel - Pata, Supansa - Angelisová, Pavla - Hořejší, Václav - Brdička, Tomáš
The effects of membrane compartmentalization of csk on TCR signaling.
Biochimica et biophysica acta. Roč. 1813, č. 2 (2010), s. 367-376. ISSN 0006-3002
R&D Projects: GA ČR GEMEM/09/E011; GA MŠMT 1M0506
Institutional research plan: CEZ:AV0Z50520514
Keywords : T-cell activation * lipid rafts * CBP
Subject RIV: EB - Genetics ; Molecular Biology

The TCR signal transduction is initiated by the activation of Src-family kinases (SFK) which phosphorylate Immunoreceptor tyrosine-based activation motifs (ITAM) present in the intracellular parts of the T-cell receptor (TCR) signaling subunits. Numerous data suggest that after stimulation TCR interacts with membrane rafts and thus it gains access to SFK and other important molecules involved in signal transduction. One of the key questions is how SFK access TCR and what is the importance of non-raft and membrane raft-associated SFK for the initiation and maintenance of the TCR signaling. To answer this question we targeted a negative regulator of SFK, C-terminal Src kinase (Csk) to membrane rafts, recently described "heavy rafts" or non-raft membrane. Our data show that only Csk targeted into "classical" raft but not to "heavy raft" or non-raft membrane effectively inhibits TCR signaling, demonstrating the critical role of membrane raft-associated SFK in this process.
Permanent Link: http://hdl.handle.net/11104/0196214