Constitutive endocytosis and degradation of the pre-T cell receptor.
Constitutive endocytosis and degradation of the pre-T cell receptor.
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DOI：
10.1084/jem.20020047
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发表时间：
2002-06-17
期刊：
影响因子：
--
通讯作者：
Grassi F
中科院分区：
文献类型：
--
作者：
Panigada M;Porcellini S;Barbier E;Hoeflinger S;Cazenave PA;Gu H;Band H;von Boehmer H;Grassi F
在胸腺基质上缺乏配体的情况下，前T细胞受体(TCR)信号的构成和信号转导与前TCR移位到质膜上的糖脂丰富的微域(RAFT)有关。在这里，我们展示了前TCR在到达细胞表面后被结构性地发送到溶酶体。细胞自主下调Pre-TCR需要激活src样激酶p56lck、肌动蛋白聚合和动力蛋白。由于在同一细胞系中表达的γδ转录因子受体没有表现出这些特征，因此结构性信号转导和降解是TCR前的一个特征。观察到蛋白适配器/泛素连接酶c-Cb1被磷酸化，并选择性地转位到TcR前表达细胞中的RAFT中，这一点也很明显--但不是γδTcR表达细胞。C-Cbl介导的泛素化在Pre-TCR降解中的作用是通过药物抑制蛋白酶体和显性负c-Cbl泛素连接酶来减少降解，以及c-Cbl缺陷小鼠未成熟胸腺细胞上Pre-TCR表面表达的增加。Pre-TCR内化是发育中T细胞表面受体低水平的重要原因，也可能是Pre-TCR功能最佳的必要条件。
The pre-T cell receptor (TCR) signals constitutively in the absence of putative ligands on thymic stroma and signal transduction correlates with translocation of the pre-TCR into glycolipid-enriched microdomains (rafts) in the plasma membrane. Here, we show that the pre-TCR is constitutively routed to lysosomes after reaching the cell surface. The cell-autonomous down-regulation of the pre-TCR requires activation of the src-like kinase p56lck, actin polymerization, and dynamin. Constitutive signaling and degradation represents a feature of the pre-TCR because the γδTCR expressed in the same cell line does not exhibit these features. This is also evident by the observation that the protein adaptor/ubiquitin ligase c-Cbl is phosphorylated and selectively translocated into rafts in pre-TCR– but not γδTCR-expressing cells. A role of c-Cbl–mediated ubiquitination in pre-TCR degradation is supported by the reduction of degradation through pharmacological inhibition of the proteasome and through a dominant-negative c-Cbl ubiquitin ligase as well as by increased pre-TCR surface expression on immature thymocytes in c-Cbl–deficient mice. The pre-TCR internalization contributes significantly to the low surface level of the receptor on developing T cells, and may in fact be a requirement for optimal pre-TCR function.
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突变动力蛋白的诱导特异性阻断内吞涂层囊泡的形成。
影响因子：
7.8
作者：
Damke, H;Baba, T;Warnock, D E;Schmid, S L
通讯作者：
Schmid, S L
DOI：
10.1084/jem.187.1.105
发表时间：
1998-01-05
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Ardouin L;Ismaili J;Malissen B;Malissen M
通讯作者：
Malissen M
影响因子：
64.5
作者：
GROETTRUP, M;UNGEWISS, K;VONBOEHMER, H
通讯作者：
VONBOEHMER, H
影响因子：
15.3
作者：
Carrasco, YR;Ramiro, AR;Toribio, ML
通讯作者：
Toribio, ML
影响因子：
30.5
作者：
Aifantis, I;Gounari, F;von Boehmer, H
通讯作者：
von Boehmer, H