期刊
NATURE IMMUNOLOGY
卷 19, 期 7, 页码 733-+出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/s41590-018-0131-1
关键词
-
类别
资金
- Coffin Childs Fund [61-1560]
- Damon Runyon Cancer Research Foundation [2198-14]
- Czech Science Foundation [BIB-09208Y]
- Howard Hughes Medical Institute
- NIH, NIAID [P01 AI09158006, R01 AI083636, P30 GM110759]
- DRC Center Grant [P30 DK063720]
T cell-antigen receptor (TCR) signaling requires the sequential activities of the kinases Lck and Zap7O. Upon TCR stimulation, Lck phosphorylates the TCR, thus leading to the recruitment, phosphorylation, and activation of Zap7O. Lck binds and stabilizes phosho-Zap7O by using its SH2 domain, and Zap7O phosphorylates the critical adaptors LAT and SLP76, which coordinate downstream signaling. It is unclear whether phosphorylation of these adaptors occurs through passive diffusion or active recruitment. We report the discovery of a conserved proline-rich motif in LAT that mediates efficient LAT phosphorylation. Lck associates with this motif via its SH3 domain, and with phospho-Zap7O via its SH2 domain, thereby acting as a molecular bridge that facilitates the colocalization of Zap70 and LAT. Elimination of this proline-rich motif compromises TCR signaling and T cell development. These results demonstrate the remarkable multifunctionality of Lck, wherein each of its domains has evolved to orchestrate a distinct step in TCR signaling.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据