Journal of Biological Chemistry
Volume 273, Issue 39, 25 September 1998, Pages 25510-25515
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CELL BIOLOGY AND METABOLISM
HBx Protein of Hepatitis B Virus Activates Jak1-STAT Signaling*

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The X-gene product (HBx) of the hepatitis B virus plays essential roles in viral replication and the generation of hepatocellular carcinoma. Although the mechanism for HBx action is unclear, HBx may exert its pleiotropic functions through the stimulation of signal transduction pathways including the Ras/mitogen-activated protein kinase cascade and/or inactivation of the p53 function. Here, we investigated whether HBx has the ability to activate the Jak-STAT signaling pathway. As a first step, we established stable cell lines constitutively expressing HBx. In these HBx-expressing stable cells, the tyrosine phosphorylation of various STATs, including STAT3 and -5, was constitutively enhanced by HBx, and the concomitant increase in STAT-dependent DNA binding and transcriptional activation was observed. Furthermore, HBx specifically elevated tyrosine phosphorylation and in vitro kinase activity of Jak1, but not Jak2 or Tyk2, through protein to protein interaction with Jak1. These results clearly establish HBx as the inducer of the Jak-STAT signaling pathway, and at the same time, HBx-mediated Jak-STAT activation may provide a novel mechanism for the pleiotropic functions of HBx, including transformation and promiscuous transcriptional activation.

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*

This work was supported in part by the Korea Green Cross Company and Grant G7 from the Korean Ministry of Science and Technology.The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.