Involvement of SHP-1 tyrosine phosphatase in TCR-mediated signaling pathways in lipid rafts

Citation
A. Kosugi et al., Involvement of SHP-1 tyrosine phosphatase in TCR-mediated signaling pathways in lipid rafts, IMMUNITY, 14(6), 2001, pp. 669-680
Citations number
40
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Immunology
Journal title
IMMUNITY
ISSN journal
1074-7613 → ACNP
Volume
14
Issue
6
Year of publication
2001
Pages
669 - 680
Database
ISI
SICI code
1074-7613(200106)14:6<669:IOSTPI>2.0.ZU;2-T
Abstract
To elucidate the process of TCR-mediated signaling pathways in lipid rafts, we constructed a chimeric molecule that localizes activated SHP-1 to rafts . Raft targeting of activated SHP-1 in Jurkat-derived transfectants complet ely inhibited the expression of CD69 and transcriptional factors after TCR cross-linking. Whereas the inducible tyrosine phosphorylation of TCR zeta a nd ZAP-70 and the kinase activity of Lck were intact, phosphorylated LAT wa s rapidly dephosphorylated by raft targeting of activated SHP-1, leading to defects in LAT activation and subsequent downstream signaling events. Intr iguingly, recruitment of endogenous SHP-1 to rafts and its association with LAT were dramatically increased after TCR engagement, suggesting that SHP- 1 is involved in raft-mediated T cell activation.