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Thymocytes are tested for productive rearrangement of the tcrb locus by expression of a pre-TCR in a process termed β-selection, which requires both Notch1 and CXCR4 signaling. It has been shown that activation of the GTPase Ras allows thymocytes to proliferate and differentiate in the absence of a Pre-TCR; the direct targets of Ras at this checkpoint have not been identified, however. Mice with a mutant allele of p110γ unable to bind active Ras revealed that CXCR4-mediated PI3K activation is Ras dependent. The Ras-p110γ interaction was necessary for efficient β-selection-promoted proliferation but was dispensable for the survival or differentiation of thymocytes. Uncoupling Ras from p110γ provides unambiguous identification of a Ras interaction required for thymic β-selection.

Original publication

DOI

10.4049/jimmunol.1101949

Type

Journal article

Journal

J Immunol

Publication Date

01/11/2011

Volume

187

Pages

4667 - 4675

Keywords

Animals, Apoptosis, CD4 Antigens, CD8 Antigens, Cell Cycle, Cell Differentiation, Cell Proliferation, Cell Survival, Cells, Cultured, Class Ib Phosphatidylinositol 3-Kinase, Gene Knock-In Techniques, Immunophenotyping, Mice, Mice, Inbred C57BL, Mice, Knockout, Receptors, Antigen, T-Cell, alpha-beta, Thymocytes, ras Proteins