HEMATOPOIESIS

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 dur-ing DN3 to DN4 transition and during positive selection. Furthermore, the differ-entiation and expansion of DN3 and DN4 thymocytes in vitro were severely im-paired. These defects corresponded to defective TCR signaling. Although RhoH is not required for TCR-induced activa-tion of ZAP70 and ZAP70-mediated activa-tion of p38, it is crucial for the tyrosine phosphorylation of LAT, PLC1, 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