Transmembrane adaptor protein PAG is a mediator of PD-1 inhibitory signaling in human T cells.

ABSTRACT: The inhibitory receptor PD-1 is expressed on T cells to inhibit select functions when ligated. The complete signaling mechanism downstream of PD-1 has yet to be uncovered. Here, we discovered phosphoprotein associated with glycosphingolipid-enriched microdomains 1 (PAG) is phosphorylated following PD-1 ligation and associate this with inhibitory T cell function. Clinical cohort analysis correlates low PAG expression with increased survival from numerous tumor types. PAG knockdown in T cells prevents PD-1-mediated inhibition of cytokine secretion, cell adhesion, CD69 expression, and ERK_204/187 phosphorylation, and enhances phosphorylation of SRC₅₂₇ following PD-1 ligation. PAG overexpression rescues these effects. In vivo, PAG contributes greatly to the growth of two m

SUBMITTER: Strazza M 

PROVIDER: S-EPMC8175585 | biostudies-literature | 2021 Jun

REPOSITORIES: biostudies-literature