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Dorn, T.* ; Kuhn, U.* ; Bungartz, G.* ; Stiller, S.* ; Bauer, M.* ; Ellwart, J.W. ; Peters, T.* ; Scharffetter-Kochanek, K.* ; Semmrich, M.* ; Laschinger, M.* ; Holzmann, B.* ; Klinkert, W.E.* ; Straten, P.T.* ; Køllgaard, T.* ; Sixt, M.* ; Brakebusch, C.*

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

Blood 109, 2346-2355 (2007)
DOI
Open Access Green as soon as Postprint is submitted to ZB.
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.
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Publication type Article: Journal article
Document type Scientific Article
ISSN (print) / ISBN 0006-4971
e-ISSN 1528-0020
Journal Blood
Quellenangaben Volume: 109, Issue: 6, Pages: 2346-2355 Article Number: , Supplement: ,
Publisher American Society of Hematology
Reviewing status Peer reviewed