| First Author | Au-Yeung BB | Year | 2010 |
| Journal | Nat Immunol | Volume | 11 |
| Issue | 12 | Pages | 1085-92 |
| PubMed ID | 21037577 | Mgi Jnum | J:167326 |
| Mgi Id | MGI:4867802 | Doi | 10.1038/ni.1955 |
| Citation | Au-Yeung BB, et al. (2010) A genetically selective inhibitor demonstrates a function for the kinase Zap70 in regulatory T cells independent of its catalytic activity. Nat Immunol 11(12):1085-92 |
| abstractText | 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. |
