title: A critical role for Rictor in T lymphopoiesis.
abstract: Apart from a critical role for Notch and pre-TCR, the signaling pathway required for T lymphopoiesis is largely unknown. Given the potential link between Notch and mammalian target of rapamycin (mTOR) signaling in cancer cells, we used mice with conditional deletion of either Raptor or Rictor genes to determine potential contribution of the mTOR complex I and II in T lymphopoiesis. Our data demonstrated that targeted mutation of Rictor in the thymocytes drastically reduced the thymic cellularity, primarily by reducing proliferation of the immature thymocytes. Rictor deficiency caused a partial block of thymocyte development at the double-negative 3 stage. The effect of Rictor deficiency is selective for the T cell lineage, as the development of B cells, erythrocytes, and myeloid cells is largely unaffected. Analysis of bone marrow chimera generated from a mixture of wild-type and Rictor-deficient hematopoietic stem cells demonstrated that the function of Rictor is cell intrinsic. These data revealed a critical function of mTOR complex 2 in T lymphopoiesis.
authors: Division of Immunotherapy, Department of Surgery, University of Michigan Medical School and Comprehensive Cancer Center, Ann Arbor, MI 48109, USA.
authors: Fei
authors: F
authors: Tang
authors: Qi
authors: Q
authors: Wu
authors: Tsuneo
authors: T
authors: Ikenoue
authors: Kun-Liang
authors: KL
authors: Guan
authors: Yang
authors: Y
authors: Liu
authors: Pan
authors: P
authors: Zheng
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D002352:Carrier Proteins / Q000276:immunology* / Q000378:metabolism; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology*; D005434:Flow Cytometry; D038041:Lymphopoiesis / Q000235:genetics / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D054504:Precursor Cells, T-Lymphoid / Q000166:cytology / Q000276:immunology*; D000076226:Rapamycin-Insensitive Companion of mTOR Protein; D060888:Real-Time Polymerase Chain Reaction; D000076223:Regulatory-Associated Protein of mTOR; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; D000076226:Rapamycin-Insensitive Companion of mTOR Protein; D000076223:Regulatory-Associated Protein of mTOR; C540162:Rptor protein, mouse; C525637:rictor protein, mouse