Involvement of SHP-1 Tyrosine Phosphatase in TCR-Mediated Signaling Pathways in Lipid Rafts

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• 作者：Atsushi Kosugi ; Junko Sakakura ; Koubun Yasuda ; Masato Ogata and Toshiyuki Hamaoka
• 刊名：Immunity
• 出版年：2001
• 出版时间：June 2001
• 年：2001
• 卷：14
• 期：6
• 页码：669-680
• 全文大小：560 K

文摘

To elucidate the process of TCR-mediated signaling pathways in lipid rafts, we constructed a chimeric molecule that localizes activated SHP-1 to rafts. Raft targeting of activated SHP-1 in Jurkat-derived transfectants completely inhibited the expression of CD69 and transcriptional factors after TCR cross-linking. Whereas the inducible tyrosine phosphorylation of TCR and ZAP-70 and the kinase activity of Lck were intact, phosphorylated LAT was rapidly dephosphorylated by raft targeting of activated SHP-1, leading to defects in LAT activation and subsequent downstream signaling events. Intriguingly, recruitment of endogenous SHP-1 to rafts and its association with LAT were dramatically increased after TCR engagement, suggesting that SHP-1 is involved in raft-mediated T cell activation.