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- Title
A genetically selective inhibitor demonstrates a function for the kinase Zap70 in regulatory T cells independent of its catalytic activity.
- Authors
Au-Yeung, Byron B; Levin, Susan E; Zhang, Chao; Hsu, Lih-Yun; Cheng, Debra A; Killeen, Nigel; Shokat, Kevan M; Weiss, Arthur
- Abstract
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.
- Publication
Nature immunology, 2010, Vol 11, Issue 12, p1085
- ISSN
1529-2916
- Publication type
Journal Article
- DOI
10.1038/ni.1955