Antigen receptor regulation of phosphoinositide-dependent kinase 1 pathways during thymocyte development
- 28 September 2006
- journal article
- Published by Wiley in FEBS Letters
- Vol. 580 (25), 5845-5850
- https://doi.org/10.1016/j.febslet.2006.09.045
Abstract
Phosphoinositide-dependent kinase 1 (PDK1) is essential for T cell development but little is know about the stimuli that regulate PDK1 signaling in vivo. The thymus contains a heterogeneous mixture of cells at different stages of development making it difficult to use biochemical techniques to examine the activity of PDK1 pathways as thymocytes develop in situ. Herein, we use a single cell assay to quantify activation of the PDK1 target kinase ribosomal S6 kinase 1 (S6K1) in different murine thymocyte subsets immediately ex vivo. This technique allows an assessment of S6K1 activation as thymocytes respond to developmental stimuli in vivo. These studies reveal that only a small percentage of thymocytes show evidence for activation of PDK1 mediated signaling in situ. The thymic subpopulations that contain active PDK1/S6K1 are those known to be responding to signaling by the pre T cell receptor and the mature alpha/beta T cell antigen receptor (TCR). Moreover, loss of antigen receptor signaling in T cell progenitors that cannot rearrange their TCR beta locus prevents in vivo activation of S6K1. The present data identifying antigen receptor signaling as a key activator of PDK1 mediated signaling afford a molecular explanation for the important role of this molecule in T cellsKeywords
This publication has 33 references indexed in Scilit:
- Induction of T cell development and establishment of T cell competence from embryonic stem cells differentiated in vitroNature Immunology, 2004
- Intracellular Location and Cell Context-Dependent Function of Protein Kinase DImmunity, 2003
- Insulin-induced Drosophila S6 kinase activation requires phosphoinositide 3-kinase and protein kinase BBiochemical Journal, 2003
- Positive and Negative Selection of T CellsAnnual Review of Immunology, 2003
- Induction of T Cell Development from Hematopoietic Progenitor Cells by Delta-like-1 In VitroImmunity, 2002
- TSC1–TSC2: a complex tale of PKB-mediated S6K regulationNature Cell Biology, 2002
- Pro-Thymocyte Expansion by c-kit and the Common Cytokine Receptor γ Chain Is Essential for Repertoire FormationImmunity, 1997
- CD 69 expression during selection and maturation of CD4+8+ thymocytesEuropean Journal of Immunology, 1993
- RAG-2-deficient mice lack mature lymphocytes owing to inability to initiate V(D)J rearrangementCell, 1992
- RAG-1-deficient mice have no mature B and T lymphocytesCell, 1992