Essential function for the GTPase TC21 in homeostatic antigen receptor signaling

Nat Immunol. 2009 Aug;10(8):880-8. doi: 10.1038/ni.1749. Epub 2009 Jun 28.


T cell antigen receptors (TCRs) and B cell antigen receptors (BCRs) transmit low-grade signals necessary for the survival and maintenance of mature cell pools. We show here that TC21, a small GTPase encoded by Rras2, interacted constitutively with both kinds of receptors. Expression of a dominant negative TC21 mutant in T cells produced a rapid decrease in cell viability, and Rras2(-/-) mice were lymphopenic, possibly as a result of diminished homeostatic proliferation and impaired T cell and B cell survival. In contrast, TC21 was overexpressed in several human lymphoid malignancies. Finally, the p110delta catalytic subunit of phosphatidylinositol-3-OH kinase (PI(3)K) was recruited to the TCR and BCR in a TC21-dependent way. Consequently, we propose TC21 directly links antigen receptors to PI(3)K-mediated survival pathways.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • B-Lymphocytes / immunology*
  • Cell Survival
  • Homeostasis
  • Humans
  • Lymph Nodes / cytology
  • Lymph Nodes / immunology
  • Lymphoma, B-Cell / immunology
  • Lymphoma, B-Cell / metabolism
  • Lymphoma, T-Cell / immunology
  • Lymphoma, T-Cell / metabolism
  • Membrane Proteins / immunology
  • Membrane Proteins / physiology*
  • Mice
  • Monomeric GTP-Binding Proteins / immunology
  • Monomeric GTP-Binding Proteins / physiology*
  • Phosphatidylinositol 3-Kinases / physiology
  • Receptors, Antigen, B-Cell / immunology
  • Receptors, Antigen, B-Cell / physiology*
  • Receptors, Antigen, T-Cell / immunology
  • Receptors, Antigen, T-Cell / physiology*
  • Signal Transduction
  • T-Lymphocytes / immunology*


  • Membrane Proteins
  • Receptors, Antigen, B-Cell
  • Receptors, Antigen, T-Cell
  • Phosphatidylinositol 3-Kinases
  • RRAS2 protein, human
  • Rras2 protein, mouse
  • Monomeric GTP-Binding Proteins