Costimulatory Role of CXCR4 with Pre-TCR and Its Crosstalk with PI3K in β-Selection of Thymocytes

Science Signaling  27 Apr 2010:
Vol. 3, Issue 119, pp. jc4
DOI: 10.1126/scisignal.3119jc4

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Chemokines were initially thought of only as regulators of the migration of developing thymocytes between different compartments of the thymus and were predicted also to be involved in early stages of thymocyte development. Recent data have suggested additional functions for the chemokine receptor CXCR4—a G protein–coupled receptor—in thymocyte development, particularly during the β-selection developmental checkpoint. Phosphotidylinositol 3-kinase interacts with the pre–T cell receptor and CXCR4 during migration, proliferation, and differentiation of developing thymocytes. CXCR4 and Notch signaling, along with inhibition of glycogen synthase kinase-3β (GSK-3β), are essential for the proliferation and differentiation of thymocytes during β-selection. Thus, a critical role of chemokines and its downstream signaling in the β-selection of thymocytes has been demonstrated.

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