Tyrosine dephosphorylation of STAT3 in SARS coronavirus-infected Vero E6 cells.
Severe acute respiratory syndrome (SARS) has become a global public health emergency. p38 mitogen-activated protein kinase (MAPK) and its downstream targets are activated in SARS coronavirus (SARS-CoV)-infected Vero E6 cells and activation of p38 MAPK enhances the cytopathic effects of SARS-CoV infection. In addition, weak activation of Akt cannot prevent SARS-CoV infection-induced apoptosis in Vero E6 cells. In the present study, we demonstrated that signal transducer and activator of transcription (STAT) 3, which is constitutively phosphorylated at tyrosine (Tyr)-705 and slightly phosphorylated at serine (Ser)-727 in Vero E6 cells, was dephosphorylated at Tyr-705 on SARS-CoV infection. In addition to phosphorylation of p38 MAPK in virus-infected cells, other MAPKs, i.e., extracellular signal-regulated kinase (ERK) 1/2 and c-Jun N-terminal kinase (JNK), were phosphorylated. Although inhibitors of ERK1/2 and JNK (PD98059 and SP600125) had no effect on phosphorylation status of STAT3, inhibitors of p38 MAPK (SB203580 and SB202190) partially inhibited dephosphorylation of STAT3 at Tyr-705. Tyr-705-phosphorylated STAT3 was localized mainly in the nucleus in mock infected cells, whereas STAT3 disappeared from the nucleus in virus-infected cells. As STAT3 acts as an activator of transcription in the nucleus, these results suggest that STAT3 lacks its activity on transcription in SARS-CoV-infected Vero E6 cells.
Mizutani
Tetsuya
T
Special Pathogens Laboratory, Department of Virology 1, National Institute of Infectious Diseases, Gakuen 4-7-1, Musashimurayama, Tokyo 208-0011, Japan. tmizutan@nih.go.jp
Fukushi
Shuetsu
S
Murakami
Masaaki
M
Hirano
Toshio
T
Saijo
Masayuki
M
Kurane
Ichiro
I
Morikawa
Shigeru
S
D000818:Animals; D002467:Cell Nucleus / Q000378:metabolism; D002522:Chlorocebus aethiops; D004268:DNA-Binding Proteins / Q000378:metabolism*; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D010766:Phosphorylation; D045473:Severe acute respiratory syndrome-related coronavirus / Q000378:metabolism*; D050796:STAT3 Transcription Factor; D015534:Trans-Activators / Q000378:metabolism*; D014443:Tyrosine / Q000378:metabolism*; D014709:Vero Cells
D004268:DNA-Binding Proteins; D050796:STAT3 Transcription Factor; D015534:Trans-Activators; D014443:Tyrosine; D020928:Mitogen-Activated Protein Kinases