期刊
NATURE IMMUNOLOGY
卷 11, 期 12, 页码 1085-U95出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/ni.1955
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- National Institute of Arthritis, Musculoskeletal and Skin Diseases, National Institutes of Health [RC2AR058947, F32AR056174]
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.
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