RhoH is important for positive thymocyte selection and T-cell receptor signaling.
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.
Dorn
Tatjana
T
Max Planck Institute of Biochemistry, Heisenberg Group Regulation of Cytoskeletal Organization, Martinsried, Germany.
Kuhn
Ursula
U
Bungartz
Gerd
G
Stiller
Sebastian
S
Bauer
Martina
M
Ellwart
Joachim
J
Peters
Thorsten
T
Scharffetter-Kochanek
Karin
K
Semmrich
Monika
M
Laschinger
Melanie
M
Holzmann
Bernhard
B
Klinkert
Wolfgang E F
WE
Straten
Per Thor
PT
Køllgaard
Tania
T
Sixt
Michael
M
Brakebusch
Cord
C
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*
D015415:Biomarkers; D018821:CD18 Antigens; D011948:Receptors, Antigen, T-Cell; C496930:RhoH protein, mouse; D014157:Transcription Factors; D020741:rho GTP-Binding Proteins; D002118:Calcium