RhoH GTPase recruits and activates Zap70 required for T cell receptor signaling and thymocyte development

Nat Immunol. 2006 Nov;7(11):1182-90. doi: 10.1038/ni1396. Epub 2006 Oct 8.


RhoH is a hematopoietic-specific, GTPase-deficient member of the Rho GTPase family with unknown physiological function. Here we demonstrate that Rhoh-/- mice have impaired T cell receptor (TCR)-mediated thymocyte selection and maturation, resulting in T cell deficiency. RhoH deficiency resulted in defective CD3zeta phosphorylation, impaired translocation of the signaling molecule Zap70 to the immunological synapse and reduced activation of Zap70-mediated signaling in thymic and peripheral T cells. Proteomic analyses demonstrated that RhoH is a component of TCR signaling and is required for recruitment of Zap70 to the TCR through interaction with RhoH noncanonical immunoreceptor tyrosine-based activation motifs (ITAMs). In vivo reconstitution studies also demonstrated that RhoH function depends on phosphorylation of the RhoH ITAMs. These findings suggest that RhoH is a critical regulator of thymocyte development and TCR signaling by mediating recruitment and activation of Zap70.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Cell Differentiation / immunology*
  • Cell Line
  • Cell Line, Tumor
  • Humans
  • Jurkat Cells
  • Lymphopenia / genetics
  • Lymphopenia / immunology
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Mice, Transgenic
  • Receptors, Antigen, T-Cell / physiology*
  • Signal Transduction / immunology*
  • Thymus Gland / cytology*
  • Thymus Gland / immunology
  • Transcription Factors / deficiency
  • Transcription Factors / genetics
  • Transcription Factors / physiology*
  • ZAP-70 Protein-Tyrosine Kinase / metabolism*
  • rho GTP-Binding Proteins / deficiency
  • rho GTP-Binding Proteins / genetics
  • rho GTP-Binding Proteins / physiology*


  • Receptors, Antigen, T-Cell
  • RhoH protein, mouse
  • Transcription Factors
  • ZAP-70 Protein-Tyrosine Kinase
  • Zap70 protein, mouse
  • rho GTP-Binding Proteins