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Interaction of Ras with p110? is required for thymic ?-selection in the mouse.

ABSTRACT: Thymocytes are tested for productive rearrangement of the tcrb locus by expression of a pre-TCR in a process termed ?-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 p110? unable to bind active Ras revealed that CXCR4-mediated PI3K activation is Ras dependent. The Ras-p110? interaction was necessary for efficient ?-selection-promoted proliferation but was dispensable for the survival or differentiation of thymocytes. Uncoupling Ras from p110? provides unambiguous identification of a Ras interaction required for thymic ?-selection.

SUBMITTER: Janas ML

PROVIDER: S-EPMC3198841 | biostudies-literature | 2011 Nov

REPOSITORIES: biostudies-literature

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Interaction of Ras with p110γ is required for thymic β-selection in the mouse.

Janas Michelle L ML Turner Martin M

Journal of immunology (Baltimore, Md. : 1950) 20110919 9

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 Ra ...[more]

PMID: 21930962

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