title: The effects of membrane compartmentalization of csk on TCR signaling.
abstract: 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. However, the precise mechanism of this process is unclear. 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.
authors.affiliation: Institute of Molecular Genetics AS CR, Prague, Czech Republic.
authors.forename: Pavel
authors.initials: P
authors.lastname: Otáhal
authors.forename: Supansa
authors.initials: S
authors.lastname: Pata
authors.forename: Pavla
authors.initials: P
authors.lastname: Angelisová
authors.forename: Václav
authors.initials: V
authors.lastname: Hořejší
authors.forename: Tomáš
authors.initials: T
authors.lastname: Brdička
mesh_terms: D000081247:CSK Tyrosine-Protein Kinase; D002462:Cell Membrane / Q000378:metabolism*; D002478:Cells, Cultured; D006801:Humans; D015151:Immunoblotting; D021962:Membrane Microdomains; D010766:Phosphorylation; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism*; D015398:Signal Transduction; D019061:src-Family Kinases
chemical_list: D011518:Proto-Oncogene Proteins; D011948:Receptors, Antigen, T-Cell; D011505:Protein-Tyrosine Kinases; D000081247:CSK Tyrosine-Protein Kinase; D019061:src-Family Kinases; C000631346:CSK protein, human