期刊
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
卷 115, 期 9, 页码 2174-2179出版社
NATL ACAD SCIENCES
DOI: 10.1073/pnas.1713301115
关键词
T cell antigen receptor; signal transduction; MAP kinase; immune synapse
资金
- Center for Cancer Research, NCI, NIH
- German Research Foundation (DFG) [GA 1818/2-1]
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.
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