| First Author | Liu C | Year | 2021 |
| Journal | Sci Adv | Volume | 7 |
| Issue | 41 | Pages | eabg6262 |
| PubMed ID | 34623920 | Mgi Jnum | J:338433 |
| Mgi Id | MGI:6787989 | Doi | 10.1126/sciadv.abg6262 |
| Citation | Liu C, et al. (2021) Glycogen synthase kinase 3 drives thymocyte egress by suppressing beta-catenin activation of Akt. Sci Adv 7(41):eabg6262 |
| abstractText | 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, beta-catenin accumulated in the cytoplasm, where it associated with and activated Akt, leading to phosphorylation and degradation of Foxo1 and downregulation of Klf2 and S1P(1) expression, thereby preventing emigration of thymocytes. A cytoplasmic membrane-localized beta-catenin excluded from the nucleus promoted Akt activation, suggesting a new function of beta-catenin independent of its role as a transcriptional activator. Furthermore, genetic ablation of beta-catenin, retroviral expression of a dominant negative Akt mutant, and transgenic expression of a constitutively active Foxo1 restored emigration of GSK3-deficient thymocytes. Our findings establish an essential role for GSK3 in thymocyte egress and reveal a previously unidentified signaling function of beta-catenin in the cytoplasm. |
