Activation of the p38 Mitogen-Activated Protein Kinase Pathway Arrests Cell Cycle Progression and Differentiation of Immature Thymocytes in Vivo
Open Access
- 17 January 2000
- journal article
- Published by Rockefeller University Press in The Journal of Experimental Medicine
- Vol. 191 (2) , 321-334
- https://doi.org/10.1084/jem.191.2.321
Abstract
The development of T cells in the thymus is coordinated by cell-specific gene expression programs that involve multiple transcription factors and signaling pathways. Here, we show that the p38 mitogen-activated protein (MAP) kinase signaling pathway is strictly regulated during the differentiation of CD4−CD8− thymocytes. Persistent activation of p38 MAP kinase blocks fetal thymocyte development at the CD25+CD44− stage in vivo, and results in the lack of T cells in the peripheral immune system of adult mice. Inactivation of p38 MAP kinase is required for further differentiation of these cells into CD4+CD8+ thymocytes. The arrest of cell cycle in mitosis is partially responsible for the blockade of differentiation. Therefore, the p38 MAP kinase pathway is a critical regulatory element of differentiation and proliferation during the early stages of in vivo thymocyte development.Keywords
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