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


Author(s): 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; Straten, Per Thor; Køllgaard, Tania; Sixt, Michael; Brakebusch, Cord
Article Title: RhoH is important for positive thymocyte selection and T-cell receptor signaling
Affiliation
Abstract: 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, PLCgamma1, 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.
Keywords: Animals; Cells, Cultured; Mice; Mice, Knockout; Cell Movement; Cell Adhesion; Antigens, CD18/metabolism; Biological Markers; Calcium/metabolism; Cell Proliferation; Hematopoiesis; Receptors, Antigen, T-Cell/*metabolism; Signal Transduction/*immunology; T-Lymphocytes/cytology/metabolism; Thymus Gland/*cytology/immunology/*metabolism; Transcription Factors/deficiency/genetics/*metabolism; rho GTP-Binding Proteins/deficiency/genetics/*metabolism
Journal Title: Blood
Volume: 109
Issue 6
ISSN: 1528-0020
Publisher: American Society of Hematology  
Publication Place: United States
Date Published: 2007-03-15
Start Page: 2346
End Page: 2355
DOI: 10.1182/blood-2006-04-019034
Open access: no