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• W2186452076 abstract "Tcellreceptor(TCR)signalinginvolvesCD4/CD8-p56lckrecruitmentof ZAP-70 to the TCR receptor, ZAP-70 phosphorylation of LAT thatis followed by LAT recruitment of the GADS-SLP-76 complex. Backregulation of ZAP-70 by SLP-76 has not been documented. In thispaper, we show that anti-CD3 induced ZAP-70 cluster formation issignificantly reduced in the absence of SLP-76 (i.e., J14 cells) and inthe presence of a mutant of SLP-76 (4KE) in Jurkat and primary Tcells. Both the number of cells with clusters and the number ofclusterspercellwerereduced.ThiseffectwasnotmediatedbySLP-76 SH2 domain binding to ZAP-70 because SLP-76 failed to pre-cipitate ZAP-70 and an inactivating SH2 domain mutation (i.e.,R448L) on SLP-76 4KE did not reverse the inhibition of ZAP-70clustering. Mutation of R448 on WT SLP-76 still supported ZAP-70clustering. Intriguingly, by contrast, LAT clustering occurred nor-mally in the absence of SLP-76, or the presence of 4KE SLP-76indicating that this transmembrane adaptor can operate indepen-dently of ZAP-70-GADS-SLP-76. Our findings reconfigure the TCRsignaling pathway by showing SLP-76 back-regulation of ZAP-70,an event that could ensure that signaling components are inbalance for optimal T cell activation." @default.
• W2186452076 created "2016-06-24" @default.
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• W2186452076 date "2010-01-01" @default.
• W2186452076 modified "2023-09-27" @default.
• W2186452076 title "SH2 domain containing leukocyte phosphoprotein of 76-kDa (SLP-76) feedback regulation of ZAP-70" @default.
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