RhoH is important for positive thymocyte selection and T-cell receptor signaling

• Published in: Blood Vol. 109; no. 6; pp. 2346 - 2355
• Main Authors: Dorn, Tatjana, Kuhn, Ursula, Bungartz, Gerd, Stiller, Sebastian, Bauer, Martina, Ellwart, Joachim, Peters, Thorsten, Scharffetter-Kochanek, Karin, Semmrich, Monika, Laschinger, Melanie, Holzmann, Bernhard, Klinkert, Wolfgang E.F., Straten, Per Thor, Køllgaard, Tania, Sixt, Michael, Brakebusch, Cord
• Format: Journal Article
• Language: English
• Published: Washington, DC Elsevier Inc 15.03.2007; The Americain Society of Hematology
• Subjects: Animals; Biological and medical sciences; Biomarkers; Calcium - metabolism; CD18 Antigens - metabolism; Cell Adhesion; Cell Movement; Cell Proliferation; Cells, Cultured; Fundamental and applied biological sciences. Psychology; Fundamental immunology; Hematopoiesis; Immunobiology; Lymphoid cells: ontogeny, maturation, markers, receptors, circulation and recirculation; Mice; Mice, Knockout; Receptors, Antigen, T-Cell - metabolism; rho GTP-Binding Proteins - deficiency; rho GTP-Binding Proteins - genetics; rho GTP-Binding Proteins - metabolism; Signal Transduction - immunology; T-Lymphocytes - cytology; T-Lymphocytes - metabolism; Thymus Gland - cytology; Thymus Gland - immunology; Thymus Gland - metabolism; Transcription Factors - deficiency; Transcription Factors - genetics; Transcription Factors - metabolism; Lymphopoiesis; T cell receptor; Thymocyte; Positive selection; Rodentia; Cell differentiation; Signal transduction; Vertebrata; Mammalia; Mouse; Hematopoiesis; Animal; T-Lymphocyte; Genetics
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood-2006-04-019034

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, PLCγ1, and Vav1 and for the activation of Erk and calcium influx. These data suggest that RhoH is important for pre–TCR and TCR signaling because it allows the efficient interaction of ZAP70 with the LAT signalosome, thus regulating thymocyte development.