ENGAGEMENT OF T-CELL RECEPTOR TRIGGERS ITS RECRUITMENT TO LOW-DENSITYDETERGENT-INSOLUBLE MEMBRANE DOMAINS

Citation
C. Montixi et al., ENGAGEMENT OF T-CELL RECEPTOR TRIGGERS ITS RECRUITMENT TO LOW-DENSITYDETERGENT-INSOLUBLE MEMBRANE DOMAINS, EMBO journal (Print), 17(18), 1998, pp. 5334-5348
Citations number
78
Categorie Soggetti
Biology,"Cell Biology
Journal title
ISSN journal
02614189
Volume
17
Issue
18
Year of publication
1998
Pages
5334 - 5348
Database
ISI
SICI code
0261-4189(1998)17:18<5334:EOTRTI>2.0.ZU;2-3
Abstract
T-cell receptors (TCRs) upon binding to peptide-MHC ligands transduce signals in T lymphocytes. Tyrosine phosphorylations in the cytoplasmic domains of the CD3 (gamma delta epsilon) and zeta subunits of the TCR complex by Src family kinases initiate the signaling cascades via doc king and activation of ZAP-70 kinase and other signaling components. W e examined the role of the low-density detergent-insoluble membranes ( DIMs) in TCR signaling. Using mouse thymocytes as a model, we characte rized the structural organization of DIMs in detail. We then demonstra ted that TCR engagement triggered an immediate increase in the amount of TCR/CD3 present in DLMs, which directly involves the engaged recept or complexes. TCR/CD3 recruitment is accompanied by the accumulation o f a series of prominent tyrosine-phosphorylated substrates and by an i ncrease of the Lck activity in DIMs. Upon TCR stimulation, the DIM-ass ociated receptor complexes are highly enriched in the hyperphosphoryla ted p23 zeta chains, contain most of the TCR/CD3-associated, phosphory lation-activated ZAP-70 kinases and seem to integrate into higher orde r, multiple tyrosine-phosphorylated substrate-containing protein compl exes. The TCR/CD3 recruitment was found to depend on the activity of S rc family kinases. We thus provide the first demonstration of recuitme nt of TCR/CD3 to DIMs upon receptor stimulation and propose it as a me chanism whereby TCR engagement is coupled to downstream signaling casc ades.