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Critical role of WNK1 in MYC-dependent early mouse thymocyte development
- Source :
- eLife, Vol 9 (2020)
- Publication Year :
- 2020
- Publisher :
- eLife Sciences Publications Ltd, 2020.
-
Abstract
- WNK1, a kinase that controls kidney salt homeostasis, also regulates adhesion and migration in CD4+ T cells. Wnk1 is highly expressed in thymocytes, and since migration is important for thymocyte maturation, we investigated a role for WNK1 in mouse thymocyte development. We find that WNK1 is required for the transition of double negative (DN) thymocytes through the β-selection checkpoint and subsequent proliferation and differentiation into double positive (DP) thymocytes. Furthermore, we show that WNK1 negatively regulates LFA1-mediated adhesion and positively regulates CXCL12-induced migration in DN thymocytes. Despite this, migration defects of WNK1-deficient thymocytes do not account for the developmental arrest. Instead, we show that in DN thymocytes WNK1 transduces pre-TCR signals via OXSR1 and STK39 kinases, and the SLC12A2 ion co-transporter that are required for post-transcriptional upregulation of MYC and subsequent proliferation and differentiation into DP thymocytes. Thus, a pathway regulating ion homeostasis is a critical regulator of thymocyte development.
Details
- Language :
- English
- ISSN :
- 2050084X
- Volume :
- 9
- Database :
- Directory of Open Access Journals
- Journal :
- eLife
- Publication Type :
- Academic Journal
- Accession number :
- edsdoj.f95f939cb2a2466a8f42bfbe5fde8c05
- Document Type :
- article
- Full Text :
- https://doi.org/10.7554/eLife.56934