title: RhoH is important for positive thymocyte selection and T-cell receptor signaling.
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.
authors.affiliation: Max Planck Institute of Biochemistry, Heisenberg Group Regulation of Cytoskeletal Organization, Martinsried, Germany.
authors.forename: Tatjana
authors.initials: T
authors.lastname: Dorn
authors.forename: Ursula
authors.initials: U
authors.lastname: Kuhn
authors.forename: Gerd
authors.initials: G
authors.lastname: Bungartz
authors.forename: Sebastian
authors.initials: S
authors.lastname: Stiller
authors.forename: Martina
authors.initials: M
authors.lastname: Bauer
authors.forename: Joachim
authors.initials: J
authors.lastname: Ellwart
authors.forename: Thorsten
authors.initials: T
authors.lastname: Peters
authors.forename: Karin
authors.initials: K
authors.lastname: Scharffetter-Kochanek
authors.forename: Monika
authors.initials: M
authors.lastname: Semmrich
authors.forename: Melanie
authors.initials: M
authors.lastname: Laschinger
authors.forename: Bernhard
authors.initials: B
authors.lastname: Holzmann
authors.forename: Wolfgang E F
authors.initials: WE
authors.lastname: Klinkert
authors.forename: Per Thor
authors.initials: PT
authors.lastname: Straten
authors.forename: Tania
authors.initials: T
authors.lastname: Køllgaard
authors.forename: Michael
authors.initials: M
authors.lastname: Sixt
authors.forename: Cord
authors.initials: C
authors.lastname: Brakebusch
mesh_terms: D000818:Animals; D015415:Biomarkers; D018821:CD18 Antigens / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D002448:Cell Adhesion; D002465:Cell Movement; D049109:Cell Proliferation; D002478:Cells, Cultured; D006410:Hematopoiesis; D051379:Mice; D018345:Mice, Knockout; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism*; D015398:Signal Transduction / Q000276:immunology*; D013601:T-Lymphocytes / Q000166:cytology / Q000378:metabolism; D013950:Thymus Gland / Q000166:cytology* / Q000276:immunology / Q000378:metabolism*; D014157:Transcription Factors / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D020741:rho GTP-Binding Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*
chemical_list: D015415:Biomarkers; D018821:CD18 Antigens; D011948:Receptors, Antigen, T-Cell; C496930:RhoH protein, mouse; D014157:Transcription Factors; D020741:rho GTP-Binding Proteins; D002118:Calcium