Dynamic association of CD45 with detergent-insoluble microdomains in T lymphocytes
Dynamic association of CD45 with detergent-insoluble microdomains in T lymphocytes
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DOI：
10.4049/jimmunol.169.9.5036
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发表时间：
2002-11-01
影响因子：
4.4
通讯作者：
Ostergaard, HL
中科院分区：
文献类型：
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作者：
Edmonds, SD;Ostergaard, HL
受体样蛋白酪氨酸磷酸酶CD 45是TCR信号转导所必需的。CD 45的底物包括蛋白酪氨酸激酶p56（lck）和p59（fyn），这两种蛋白酪氨酸激酶都被证明富含洗涤剂不溶性微区。在这里，我们发现，有一个胆固醇依赖性的协会之间的CD 45和筏相关的蛋白连接器的T细胞的活化，这表明CD 45和连接器的T细胞的活化可能共定位在脂筏。与这一观察结果一致，我们发现，在Triton X-100不溶性的蔗糖梯度浮力部分中可以检测到约5%的总CD 45，表明CD 45并不被排除在脂筏之外。在用抗CD 3刺激T细胞后，发现与脂筏相关的CD 45的量减少。我们的数据表明，CD 45是目前在T细胞的脂筏活化前，也许激活筏相关的p56（lck），允许膜近端信号事件进行。此外，CD 3刺激后脂筏中CD 45含量的减少可能有助于限制脂筏中活化的p56（lck）的量，从而可能限制T细胞应答的持续时间。
The receptor-like protein tyrosine phosphatase CD45 is essential for TCR signal transduction. Substrates of CD45 include the protein tyrosine kinases p56(lck) and p59(fyn), both of which have been shown to be enriched in detergent-insoluble microdomains. Here we find that there is a cholesterol-dependent association between CD45 and the raft-associated protein linker for activation of T cells, suggesting that CD45 and linker for activation of T cells may colocalize in lipid rafts. Consistent with this observation, we find that similar to5% of total CD45 can be detected in Triton X-100-insoluble buoyant fractions of sucrose gradients, demonstrating that CD45 is not excluded from lipid rafts. Upon stimulation of T cells with anti-CD3, there is a reduction in the amount of CD45 found associating with lipid rafts. Our data suggest that CD45 is present in lipid rafts in T cells before activation, perhaps to activate raft-associated p56(lck), allowing membrane-proximal signaling events to proceed. Furthermore, the reduction in CD45 content of lipid rafts after CD3 stimulation may serve to limit the amounts of activated p56(lck) in rafts and thus possibly the duration of T cell responses.