Glycogen synthase kinase 3 drives thymocyte egress by suppressing β-catenin activation of Akt.

ABSTRACT: Molecular pathways controlling emigration of mature thymocytes from thymus to the periphery remain incompletely understood. Here, we show that T cell–specific ablation of glycogen synthase kinase 3 (GSK3) led to severely impaired thymic egress. In the absence of GSK3, β-catenin accumulated in the cytoplasm, where it associated with and activated Akt, leading to phosphorylation and degradation of Foxo1 and downregulation of Klf2 and S1P₁ expression, thereby preventing emigration of thymocytes. A cytoplasmic membrane-localized β-catenin excluded from the nucleus promoted Akt activation, suggesting a new function of β-catenin independent of its role as a transcriptional activator. Furthermore, genetic ablation of β-catenin, retroviral expression of a dominant negative Akt mutant, a

SUBMITTER: Liu C 

PROVIDER: S-EPMC8500522 | biostudies-literature | 2021 Oct

REPOSITORIES: biostudies-literature