Through induction of juxtaposition and tyrosine kinase activity of Jak1, X-gene product of hepatitis B virus stimulates Ras and the transcriptional activation through AP-1, NF-kappaB, and SRE enhancers.
Here, based on the recent finding of HBx (X-gene product of hepatitis B virus) as the inducer of Jak1, we investigated the mechanism for the HBx-mediated host cell regulation and found that (i) HBx associates specifically with Jak1 in vivo; (ii) HBx itself forms a dimer which leads to juxtaposition of associated Jak1 and subsequent activation of the tyrosine kinase activity of Jak1; (iii) HBx-mediated activation of the promoters containing AP-1-, NF-kappaB-, SRE-, and SIE-sites is dependent on the activation of Jak1; (iv) Jak1, once activated by HBx, induces Ras activity through recruitment of Grb2 and induces tyrosine phosphorylation of Raf1, but not shc. These findings show that previously reported functions of HBx, such as activation of multiple signaling pathways and transcriptional activation are attributable to HBx-mediated Jak1 activation.
Kim
H
H
Division of Molecular Life Science and Center for Cell Signaling Research, Ewha Woman's University, 11-1 Daehyundong, Seoul, Seodaemoongu, 120-750, Korea.
Lee
Y H
YH
Won
J
J
Yun
Y
Y
D048868:Adaptor Proteins, Signal Transducing; D033942:Adaptor Proteins, Vesicular Transport; D015153:Blotting, Western; D002460:Cell Line; D004268:DNA-Binding Proteins / Q000378:metabolism*; D019281:Dimerization; D004789:Enzyme Activation; D005656:Fungal Proteins; D050980:GATA Transcription Factors; D051380:GRB2 Adaptor Protein; D006515:Hepatitis B virus / Q000378:metabolism*; D006801:Humans; D053613:Janus Kinase 1; D008099:Liver / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism*; D010766:Phosphorylation; D010957:Plasmids / Q000378:metabolism; D011233:Precipitin Tests; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D011506:Proteins / Q000378:metabolism; D019908:Proto-Oncogene Proteins c-raf / Q000378:metabolism; D016392:Proto-Oncogene Proteins pp60(c-src) / Q000378:metabolism; D055765:Shc Signaling Adaptor Proteins; D015398:Signal Transduction; D000071425:Src Homology 2 Domain-Containing, Transforming Protein 1; D015534:Trans-Activators / Q000378:metabolism* / Q000502:physiology*; D018808:Transcription Factor AP-1 / Q000378:metabolism*; D014158:Transcription, Genetic; D015533:Transcriptional Activation; D014443:Tyrosine / Q000378:metabolism; D054334:Viral Regulatory and Accessory Proteins; D018631:ras Proteins / Q000378:metabolism*
D048868:Adaptor Proteins, Signal Transducing; D033942:Adaptor Proteins, Vesicular Transport; D004268:DNA-Binding Proteins; D005656:Fungal Proteins; D050980:GATA Transcription Factors; D051380:GRB2 Adaptor Protein; C495948:GRB2 protein, human; D016328:NF-kappa B; D011506:Proteins; C528024:SHC1 protein, human; D055765:Shc Signaling Adaptor Proteins; D000071425:Src Homology 2 Domain-Containing, Transforming Protein 1; C115209:Sre protein, Neurospora crassa; D015534:Trans-Activators; D018808:Transcription Factor AP-1; D054334:Viral Regulatory and Accessory Proteins; C057628:hepatitis B virus X protein; D014443:Tyrosine; D011505:Protein-Tyrosine Kinases; C507904:JAK1 protein, human; D053613:Janus Kinase 1; D016392:Proto-Oncogene Proteins pp60(c-src); D019908:Proto-Oncogene Proteins c-raf; D018631:ras Proteins