The costimulatory activity of Tim-3 requires Akt and MAPK signaling and its recruitment to the immune synapse.

ABSTRACT: Expression of the transmembrane protein Tim-3 is increased on dysregulated T cells undergoing chronic activation, including during chronic infection and in solid tumors. Thus, Tim-3 is generally thought of as an inhibitory protein. We and others previously reported that under some circumstances, Tim-3 exerts paradoxical costimulatory activity in T cells (and other cells), including enhancement of the phosphorylation of ribosomal S6 protein. Here, we examined the upstream signaling pathways that control Tim-3-mediated increases in phosphorylated S6 in T cells. We also defined the localization of Tim-3 relative to the T cell immune synapse and its effects on downstream signaling. Recruitment of Tim-3 to the immune synapse was mediated exclusively by the transmembrane domain, replacement of w

SUBMITTER: Kataoka S 

PROVIDER: S-EPMC9741863 | biostudies-literature | 2021 Jun

REPOSITORIES: biostudies-literature