Searching across hundreds of databases

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.

Nature immunology | Dec 16, 2010

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 RIS Download

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

Research resources used in this publication

None found

Research tools detected in this publication

None found

Data used in this publication

None found

Associated grants

  • Agency: NIAMS NIH HHS, Id: K01 AR060807
  • Agency: NIAMS NIH HHS, Id: F32 AR056174
  • Agency: NIAMS NIH HHS, Id: RC2 AR058947
  • Agency: NIAMS NIH HHS, Id: RC2AR058947
  • Agency: NIAMS NIH HHS, Id: F32AR056174

Publication data is provided by the National Library of Medicine ® and PubMed ®. Data is retrieved from PubMed ® on a weekly schedule. For terms and conditions see the National Library of Medicine Terms and Conditions.

We have not found any resources mentioned in this publication.