Yan Guangrong, Luo Wei, Lu Zhongxin, Luo Xiangjian, Li Lili, Liu Sufang, Liu Yiping, Tang Min, Dong Zigang, Cao Ya
Cancer Research Institute, Xiangya School of Medicine, Central South University, 110 Xiangya Road, Changsha, Hunan 410078, China.
Cell Signal. 2007 Feb;19(2):341-8. doi: 10.1016/j.cellsig.2006.07.019. Epub 2006 Aug 3.
We have previously combined phosphorylation enrichment with proteomics technology to elucidate the novel phosphoproteins in the signaling pathways triggered by Epstein-Barr virus (EBV)-encoded latent membrane protein 1 (LMP1) and shown that LMP1 can increase the phosphorylation level of annexin A2. Here, we further showed that LMP1 increased the serine, but not tyrosine, phosphorylation of annexin A2 by activating a novel signaling pathway, the protein kinase C (PKC) signaling pathway. However, LMP1 did not affect the level of annexin A2 expression. In addition, we found that LMP1 induced the nuclear entry of annexin A2 in an energy- and temperature-dependent manner, suggesting that the nuclear entry of annexin A2 is an active process. Treatment of LMP1-expressing cells with the PKC inhibitor myr-psiPKC resulted in annexin A2 being present almost exclusively at cell surface, instead of within the nucleus, suggesting that the nuclear entry of annexin A2 was associated with serine phosphorylation mediated by PKC.
我们之前将磷酸化富集与蛋白质组学技术相结合，以阐明由爱泼斯坦-巴尔病毒（EBV）编码的潜伏膜蛋白1（LMP1）触发的信号通路中的新型磷酸化蛋白，并表明LMP1可增加膜联蛋白A2的磷酸化水平。在此，我们进一步表明，LMP1通过激活一种新型信号通路——蛋白激酶C（PKC）信号通路，增加了膜联蛋白A2的丝氨酸而非酪氨酸磷酸化。然而，LMP1并不影响膜联蛋白A2的表达水平。此外，我们发现LMP1以能量和温度依赖的方式诱导膜联蛋白A2进入细胞核，这表明膜联蛋白A2进入细胞核是一个活跃的过程。用PKC抑制剂myr-psiPKC处理表达LMP1的细胞，导致膜联蛋白A2几乎只存在于细胞表面，而不是细胞核内，这表明膜联蛋白A2进入细胞核与PKC介导的丝氨酸磷酸化有关。
