A novel functional interaction between Vav and PKCθ is required for TCR-induced T cell activation

A novel functional interaction between Vav and PKCθ is required for TCR-induced T cell activation
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DOI:
10.1016/s1074-7613(00)80168-5
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发表时间:
2000-02-01
期刊:
影响因子:
32.4
通讯作者:
Altman, A
Altman, A
中科院分区:
医学1区
文献类型:
--
作者:
Villalba, M;Coudronniere, N;Altman, A

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Vav和PKC θ在TCR/CD 28诱导的MAP激酶刺激和IL-2基因活化中起早期和重要的作用。Vav对于肌动蛋白细胞骨架重组和TCR加帽也至关重要。在这里,我们报告说,PKC θ功能的选择性需要在Vav信号通路介导的TCR/CD 28诱导的激活JNK和IL-2基因和上调CD 69的表达。Vav还促进PKC θ从胞质溶胶易位到膜和细胞骨架,并在依赖于Rac和肌动蛋白细胞骨架重组的CD 3/CD 28启动的途径中诱导其酶促活化。这些发现揭示了Vav/Rac通路促进PKC θ向T细胞突触的募集及其活化,这是T细胞活化和IL-2产生的必要过程。
Vav and PKC theta play an early and important role in the TCR/CD28-induced stimulation of MAP kinases and activation of the IL-2 gene. Vav is also essential for actin cytoskeleton reorganization and TCR capping. Here, we report that PKC theta function was selectively required in a Vav signaling pathway that mediates the TCR/CD28-induced activation of JNK and the IL-2 gene and the upregulation of CD69 expression. Vav also promoted PKC theta translocation from the cytosol to the membrane and cytoskeleton and induced its enzymatic activation in a CD3/CD28-initiated pathway that was dependent on Rac and on actin cytoskeleton reorganization. These findings reveal that the Vav/Rac pathway promotes the recruitment of PKC theta to the T cell synapse and its activation, essential processes for T cell activation and IL-2 production.