ZAP-70对Vav-SLP-76结合的调节及其与白细胞介素-2的TCR ζ/CD3诱导的相关性。

Regulation of Vav-SLP-76 binding by ZAP-70 and its relevance to TCR zeta/CD3 induction of interleukin-2.

作者信息

Raab M, da Silva A J, Findell P R, Rudd C E

机构信息

Division of Tumor Immunology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts 02115, USA.

出版信息

Immunity. 1997 Feb;6(2):155-64. doi: 10.1016/s1074-7613(00)80422-7.

DOI:10.1016/s1074-7613(00)80422-7

PMID:9047237

Abstract

T cell activation stimulates p56(lck), p59(fyn), ZAP-70, Vav-SLP-76 binding, and IL-2 transcription. Major questions concern the tyrosine-kinase and relevant site(s) needed for Vav-SLP-76 complex formation and its role in IL-2 production. Here, we show that of the three kinases, only ZAP-70 phosphorylates SLP-76 at specific sites that allow Vav SH2 domain binding. Therefore, while p56(lck) regulates proximal events, ZAP-70 acts downstream on targets such as SLP-76. We also show by in vitro and in vivo analysis that two SLP-76 pYESP motifs (Y113 and Y128) mediate binding, the first being more efficient. A third pYEPP motif (Y145) failed to bind. Finally, TCR zeta CD3 ligation of T cell hybridoma DC27.10 induces IL-2 production without detectable Vav-SLP-76 binding. Therefore, despite effects of Vav-SLP-76 on IL-2 expression, Vav-SLP-76 binding per se is not essential for IL-2 production in all T cells.

摘要

T细胞活化刺激p56(lck)、p59(fyn)、ZAP - 70、Vav - SLP - 76结合以及白细胞介素-2（IL - 2）转录。主要问题涉及Vav - SLP - 76复合物形成所需的酪氨酸激酶和相关位点及其在IL - 2产生中的作用。在此，我们表明在这三种激酶中，只有ZAP - 70在特定位点磷酸化SLP - 76，这些位点允许Vav SH2结构域结合。因此，虽然p56(lck)调节近端事件，但ZAP - 70作用于诸如SLP - 76等靶点的下游。我们还通过体外和体内分析表明，两个SLP - 76的pYESP基序（Y113和Y128）介导结合，第一个更有效。第三个pYEPP基序（Y145）未能结合。最后，T细胞杂交瘤DC27.10的TCR ζ CD3连接诱导IL - 2产生，而未检测到Vav - SLP - 76结合。因此，尽管Vav - SLP - 76对IL - 2表达有影响，但Vav - SLP - 76结合本身对于所有T细胞中IL - 2的产生并非必不可少。