Epstein-Barr virus latent membrane protein 1 mediates phosphorylation and nuclear translocation of annexin A2 by activating PKC pathway.
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.
Yan
Guangrong
G
Cancer Research Institute, Xiangya School of Medicine, Central South University, 110 Xiangya Road, Changsha, Hunan 410078, China.
Luo
Wei
W
Lu
Zhongxin
Z
Luo
Xiangjian
X
Li
Lili
L
Liu
Sufang
S
Liu
Yiping
Y
Tang
Min
M
Dong
Zigang
Z
Cao
Ya
Y
D021581:Active Transport, Cell Nucleus; D017306:Annexin A2 / Q000378:metabolism*; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000378:metabolism* / Q000821:virology; D004734:Energy Metabolism; D006801:Humans; D010766:Phosphorylation; D011493:Protein Kinase C / Q000378:metabolism*; D012694:Serine / Q000737:chemistry; D015398:Signal Transduction; D013696:Temperature; D014443:Tyrosine / Q000737:chemistry; D014763:Viral Matrix Proteins / Q000378:metabolism* / Q000502:physiology
D017306:Annexin A2; C037662:EBV-associated membrane antigen, Epstein-Barr virus; D014763:Viral Matrix Proteins; D014443:Tyrosine; D012694:Serine; D011493:Protein Kinase C