國家衛生研究院 NHRI:Item 3990099045/6734
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    題名: Attenuation of T cell receptor signaling by serine phosphorylation-mediated lysine 30 ubiquitination of SLP-76 protein
    作者: Wang, X;Li, JP;Chiu, LL;Lan, JL;Chen, DY;Boomer, J;Tan, TH
    貢獻者: Immunology Research Center
    摘要: Src homology 2 (SH2) domain-containing leukocyte protein of 76 kDa (SLP-76) is an adaptor protein that is essential for T cell development and T cell receptor (TCR) signaling activation. Previous studies have identified an important negative feedback regulation of SLP-76 by hematopoietic progenitor kinase 1 (HPK1, MAP4K1)-induced Ser-376 phosphorylation. Ser-376 phosphorylation of SLP-76 mediates 14-3-3 binding, resulting in the attenuation of SLP-76 activation and downstream signaling; however, the underlying mechanism of this action remains unknown. Here we report that the phosphorylated SLP-76 is ubiquitinated and targeted for proteasomal degradation during TCR signaling. SLP-76 ubiquitination is mediated by Ser-376 phosphorylation. Furthermore, Lys-30 is identified as an ubiquitination site of SLP-76. Loss of Lys-30 ubiquitination of SLP-76 results in enhanced anti-CD3-induced ERK and JNK activation. These results reveal a novel regulation mechanism of SLP-76 by ubiquitination and proteasomal degradation of the activated SLP-76, which is mediated by Ser-376 phosphorylation, leading to downregulation of TCR signaling.
    日期: 2012-10-05
    關聯: Journal of Biological Chemistry. 2012 Oct 5;287(41):34091-34100.
    Link to: http://dx.doi.org/10.1074/jbc.M112.371062
    JIF/Ranking 2023: http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=1083-351X&DestApp=IC2JCR
    Cited Times(WOS): https://www.webofscience.com/wos/woscc/full-record/WOS:000309654200015
    Cited Times(Scopus): http://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=84867241759
    顯示於類別:[譚澤華] 期刊論文

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