Preparing your results

Our searching services are busy right now. Your search will reload in five seconds.

Forgot Password

If you have forgotten your password you can enter your email here and get a temporary password sent to your email.

A genetically selective inhibitor demonstrates a function for the kinase Zap70 in regulatory T cells independent of its catalytic activity.

To investigate the role of the kinase Zap70 in T cells, we generated mice expressing a Zap70 mutant whose catalytic activity can be selectively blocked by a small-molecule inhibitor. We found that conventional naive, effector and memory T cells were dependent on the kinase activity of Zap70 for their activation, which demonstrated a nonredundant role for Zap70 in signals induced by the T cell antigen receptor (TCR). In contrast, the catalytic activity of Zap70 was not required for activation of the GTPase Rap1 and inside-out signals that promote integrin adhesion. This Zap70 kinase-independent pathway was sufficient for the suppressive activity of regulatory T cells (T(reg) cells), which was unperturbed by inhibition of the catalytic activity of Zap70. Our results indicate Zap70 is a likely therapeutic target.

Pubmed ID: 21037577


  • Au-Yeung BB
  • Levin SE
  • Zhang C
  • Hsu LY
  • Cheng DA
  • Killeen N
  • Shokat KM
  • Weiss A


Nature immunology

Publication Data

December 16, 2010

Associated Grants

  • Agency: NIAMS NIH HHS, Id: F32 AR056174
  • Agency: NIAMS NIH HHS, Id: F32AR056174
  • Agency: NIAMS NIH HHS, Id: RC2 AR058947
  • Agency: NIAMS NIH HHS, Id: RC2AR058947

Mesh Terms

  • Animals
  • Biocatalysis
  • Cell Proliferation
  • Cell Separation
  • Enzyme Inhibitors
  • Flow Cytometry
  • Immunoblotting
  • Immunoprecipitation
  • Lymphocyte Activation
  • Mice
  • Mice, Transgenic
  • Pyrazoles
  • Pyrimidines
  • Receptors, Antigen, T-Cell
  • Signal Transduction
  • T-Lymphocytes, Regulatory
  • ZAP-70 Protein-Tyrosine Kinase