Matches in SemOpenAlex for { <https://semopenalex.org/work/W2898535519> ?p ?o ?g. }
- W2898535519 endingPage "e0206232" @default.
- W2898535519 startingPage "e0206232" @default.
- W2898535519 abstract "Programmed cell death-1 (PD-1) is an inhibitory immune checkpoint receptor that negatively regulates the functioning of T cell. Although the direct targets of PD-1 were not identified, its inhibitory action on the TCR signaling pathway was known much earlier. Recent experiments suggest that the PD-1 inhibits the TCR and CD28 signaling pathways at a very early stage ─ at the level of phosphorylation of the cytoplasmic domain of TCR and CD28 receptors. Here, we develop a mathematical model to investigate the influence of inhibitory effect of PD-1 on the activation of early TCR and CD28 signaling molecules. Proposed model recaptures several quantitative experimental observations of PD-1 mediated inhibition. Model simulations show that PD-1 imposes a net inhibitory effect on the Lck kinase. Further, the inhibitory effect of PD-1 on the activation of TCR signaling molecules such as Zap70 and SLP76 is significantly enhanced by the PD-1 mediated inhibition of Lck. These results suggest a critical role for Lck as a mediator for PD-1 induced inhibition of TCR signaling network. Multi parametric sensitivity analysis explores the effect of parameter uncertainty on model simulations." @default.
- W2898535519 created "2018-11-02" @default.
- W2898535519 creator A5061612567 @default.
- W2898535519 creator A5069023830 @default.
- W2898535519 date "2018-10-24" @default.
- W2898535519 modified "2023-10-12" @default.
- W2898535519 title "Mathematical modeling identifies Lck as a potential mediator for PD-1 induced inhibition of early TCR signaling" @default.
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- W2898535519 doi "https://doi.org/10.1371/journal.pone.0206232" @default.