RETRACTED: Spike protein of SARS‐CoV stimulates cyclooxygenase‐2 expression via both calcium‐dependent and calcium‐independent protein kinase C pathways

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Abstract
We have previously shown that the nucleocapsid protein of SARS‐associated coronavirus (SARS‐CoV) activated cyclooxygenase‐2 (COX‐2) expression (1). In this study, we identified another viral protein, the spike of SARS‐CoV, which played an important role in virus‐stimulated COX‐2 expression after screening all genes from the SARS‐CoV genome. We found that an upstream calcium‐dependent PKC isozyme PKCα that modulates the downstream ERK/ NF‐κB pathway through an influx of extracellular Ca2+ is induced by the spike protein of SARS‐CoV. The ERK/NF‐κB was identified to be involved in the activation of COX‐2 promoter and production of COX‐2 protein in HEK293T cells. We also demonstrated that another unusual pathway, the calcium‐independent PI3K/PKCε/JNK/CREB pathway, functioned in cooperation with the calcium‐dependent pathway to induce COX‐2 expression upon stimulation by spike protein. This pathway can be blocked by PKCε‐specific, small interfering RNA, PI3K/JNK kinase‐specific inhibitors as well as dominant negative JNK. PKCε‐specific siRNA also attenuated the phosphorylation of JNK. Our results provide evidence that helps us understand the function of SRAS‐CoV spike protein in SARS pathogenesis.—Liu, M., Yang, Y., Gu, C., Yue, Y., Wu, K. K., Wu, J., Zhu, Y. Spike protein of SARS‐CoV stimulates cyclo‐oxygenase‐2 expression via both calcium‐dependent and calcium‐independent protein kinase C pathways. FASEB J. 21, 1586–1596 (2007)
Funding Information
  • National Natural Science Foundation of China (30570066)
  • Ministry of Education of the People's Republic of China (20050486012)