文章基本信息

标题：Intensity and duration of TCR signaling is limited by p38 phosphorylation of ZAP-70T293 and destabilization of the signalosome
作者：Maria Letizia Giardino Torchia ; Debjani Dutta ; Paul R. Mittelstadt 等
期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2018
卷号：115
期号：9
页码：2174-2179
DOI：10.1073/pnas.1713301115
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：ZAP-70 is a tyrosine kinase that is essential for initiation of T cell antigen receptor (TCR) signaling. We have found that T cell p38 MAP kinase (MAPK), which is directly phosphorylated and activated by ZAP-70 downstream of the TCR, in turn phosphorylates Thr-293 in the interdomain B region of ZAP-70. Mutant T cells expressing ZAP-70 with an alanine substitution at this residue (ZAP-70^T293A) had enhanced TCR proximal signaling and increased effector responses. Lack of ZAP-70^T293 phosphorylation increased association of ZAP-70 with the TCR and prolonged the existence of TCR signaling microclusters. These results identify a tight negative feedback loop in which ZAP-70–activated p38 reciprocally phosphorylates ZAP-70 and destabilizes the signaling complex.
关键词：T cell antigen receptor ; signal transduction ; MAP kinase ; immune synapse