title: Interaction of Ras with p110γ is required for thymic β-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 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.
authors.affiliation: Laboratory of Lymphocyte Signalling and Development, The Babraham Institute, Cambridge CB22 3AT, United Kingdom.
authors.forename: Michelle L
authors.initials: ML
authors.lastname: Janas
authors.forename: Martin
authors.initials: M
authors.lastname: Turner
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000235:genetics / Q000276:immunology; D015704:CD4 Antigens / Q000096:biosynthesis / Q000235:genetics; D016827:CD8 Antigens / Q000096:biosynthesis / Q000235:genetics; D002453:Cell Cycle / Q000235:genetics / Q000276:immunology; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology*; D049109:Cell Proliferation; D002470:Cell Survival / Q000235:genetics / Q000276:immunology; D002478:Cells, Cultured; D058544:Class Ib Phosphatidylinositol 3-Kinase / Q000172:deficiency / Q000378:metabolism* / Q000502:physiology; D055879:Gene Knock-In Techniques; D016130:Immunophenotyping; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D060168:Thymocytes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism*; D018631:ras Proteins / Q000172:deficiency / Q000378:metabolism / Q000502:physiology*
chemical_list: D015704:CD4 Antigens; D016827:CD8 Antigens; D016693:Receptors, Antigen, T-Cell, alpha-beta; D058544:Class Ib Phosphatidylinositol 3-Kinase; C546764:Pik3cg protein, mouse; D018631:ras Proteins