期刊
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH
卷 1813, 期 2, 页码 367-376出版社
ELSEVIER SCIENCE BV
DOI: 10.1016/j.bbamcr.2010.12.003
关键词
Lipid rafts; T-cell receptor; Lck; Csk
资金
- Academy of Sciences of the Czech Republic [AV0Z50520514]
- GACR [MEM/09/E011]
- Center of Molecular and Cellular Immunology, Ministry of Education, Youth and Sports of the Czech Republic [1M0506]
- Royal Golden Jubilee Ph.D. program [PHD/0035/2549]
The TCR signal transduction is initiated by the activation of Src-family kinases (SFK) which phosphorylate lmmunoreceptor 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 SF}(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. (C) 2010 Elsevier B.V. All rights reserved.
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