hnRNP-K is a nuclear target of TCR-activated ERK and required for T-cell late activation
hnRNP-K is a nuclear target of TCR-activated ERK and required for T-cell late activation
复制标题
DOI：
10.1093/intimm/dxp106
复制
发表时间：
2009-12-01
影响因子：
4.4
通讯作者：
Iwashima, Makio
中科院分区：
文献类型：
--
作者：
Chang, Jing-Wen;Koike, Toru;Iwashima, Makio
持续的细胞外信号调节激酶(ERK)信号在T细胞介导的IL-2的产生中起着关键作用。尽管已知ERK的许多下游靶点，但关于哪些分子在IL-2产生中发挥功能作用的细节仍不清楚。在这里，我们通过对TCR激活的T细胞的核蛋白进行蛋白质组学分析来解决这个问题，并确定hnRNP-K是产生IL-2所必需的ERK靶点之一。HnRNP-K是ERK的直接底物，与多种信号蛋白以及DNA和RNA形成复合体。我们的数据显示，在TCR刺激后，一种形式的hnRNP-K明显依赖于ERK的增加。小干扰RNA介导的hnRNP-K基因表达下调可抑制T细胞产生IL-2。此外，hnRNP-K表达的降低导致hnRNP-K的结合靶点Vav1的蛋白分解显著增加。由于Vav1是T细胞激活所必需的分子，数据提示ERK信号通路是T细胞激活所必需的，部分是通过抑制激活诱导的Vav1的蛋白分解。
Sustained extracellular signal-regulated kinase (ERK)-signaling plays a critical role in T-cell-mediated IL-2 production. Although many downstream targets are known for ERK, details remain unknown about which molecules play functional roles in IL-2 production. Here, we addressed this question using proteomic analysis of nuclear proteins from TCR-activated T cells and identified hnRNP-K as one of the ERK targets essential for IL-2 production. hnRNP-K was previously shown by others to be a direct substrate of ERK and form complexes with multiple signaling proteins as well as DNA and RNA. Our data showed a clear ERK-dependent increase in one form of hnRNP-K after TCR stimulation. Small interfering RNA-mediated gene knockdown of hnRNP-K expression abrogated IL-2 production by T cells. Moreover, reduction of hnRNP-K expression caused a notable increase in proteolysis of Vav1, a binding target of hnRNP-K. Since Vav1 is an essential molecule for T-cell activation, the data suggest that ERK signaling is required for T-cell activation partly by inhibiting activation-induced proteolysis of Vav1.