RhoH regulates subcellular localization of ZAP-70 and Lck in T cell receptor signaling.

ABSTRACT: RhoH is an hematopoietic-specific, GTPase-deficient Rho GTPase that plays a role in T development. We investigated the mechanisms of RhoH function in TCR signaling. We found that the association between Lck and CD3? was impaired in RhoH-deficient T cells, due to defective translocation of both Lck and ZAP-70 to the immunological synapse. RhoH with Lck and ZAP-70 localizes in the detergent-soluble membrane fraction where the complex is associated with CD3? phosphorylation. To determine if impaired translocation of ZAP-70 was a major determinant of defective T cell development, Rhoh(-/-) bone marrow cells were transduced with a chimeric myristoylation-tagged ZAP-70. Myr-ZAP-70 transduced cells partially reversed the in vivo defects of RhoH-associated thymic development and TCR signaling. Together, our results suggest that RhoH regulates TCR signaling via recruitment of ZAP-70 and Lck to CD3? in the immunological synapse. Thus, we define a new function for a RhoH GTPase as an adaptor molecule in TCR signaling pathway.

SUBMITTER: Chae HD 

PROVIDER: S-EPMC2980477 | biostudies-literature | 2010 Nov

REPOSITORIES: biostudies-literature