PD-1 inhibits T-cell receptor induced phosphorylation of the ZAP70/CD3zeta signalosome and downstream signaling to PKCtheta.
FEBS Lett
; 574(1-3): 37-41, 2004 Sep 10.
Article
in En
| MEDLINE
| ID: mdl-15358536
ABSTRACT
Engagement of the immunoinhibitory receptor, programmed death-1 (PD-1) attenuates T-cell receptor (TCR)-mediated activation of IL-2 production and T-cell proliferation. Here, we demonstrate that PD-1 modulation of T-cell function involves inhibition of TCR-mediated phosphorylation of ZAP70 and association with CD3zeta. In addition, PD-1 signaling attenuates PKCtheta activation loop phosphorylation in a cognate TCR signal. PKCtheta has been shown to be required for T-cell IL-2 production. A phosphorylated PD-1 peptide, corresponding to the C-terminal immunoreceptor tyrosine-switch motif (ITSM), acts as a docking site in vitro for both SHP-2 and SHP-1, while the phosphorylated peptide containing the N-terminal PD-1 immunoreceptor tyrosine based inhibitory motif (ITIM) associates only with SHP-2.
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Collection:
01-internacional
Database:
MEDLINE
Main subject:
Protein Kinase C
/
Protein-Tyrosine Kinases
/
Receptors, Antigen, T-Cell
/
Signal Transduction
/
Isoenzymes
/
Antigens, Surface
Limits:
Humans
Language:
En
Journal:
FEBS Lett
Year:
2004
Document type:
Article
Affiliation country:
United States