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Blood, 15 March 2007, Vol. 109, No. 6, pp. 2346-2355. Prepublished online as a Blood First Edition Paper on November 21, 2006; DOI 10.1182/blood-2006-04-019034.
HEMATOPOIESIS RhoH is important for positive thymocyte selection and T-cell receptor signaling1 Max Planck Institute of Biochemistry, Heisenberg Group Regulation of Cytoskeletal Organization, Martinsried, Germany; 2 Department of Molecular Pathology, University of Copenhagen, Denmark; 3 Department of Molecular Medicine, Max Planck Institute of Biochemistry, Martinsried, Germany; 4 GSF, Institute of Molecular Immunology, München, Germany; 5 University of Ulm, Clinic for Dermatology and Allergology, Germany; 6 Department of Surgery, Technische Universität München, Germany; 7 Department of Neuroimmunology, Max Planck Institute of Neurobiology, Martinsried, Germany; 8 Department of Hematology, Center for Cancer Immunotherapy, University Hospital Herlev, Denmark
RhoH is a small GTPase expressed only in the hematopoietic system. With the use of mice with targeted disruption of the RhoH gene, we demonstrated that RhoH is crucial for thymocyte maturation during DN3 to DN4 transition and during positive selection. Furthermore, the differentiation and expansion of DN3 and DN4 thymocytes in vitro were severely impaired. These defects corresponded to defective TCR signaling. Although RhoH is not required for TCR-induced activation of ZAP70 and ZAP70-mediated activation of p38, it is crucial for the tyrosine phosphorylation of LAT, PLC
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