Journal article
Activation of Focal Adhesion Kinase by Hepatitis B Virus HBx Protein: Multiple Functions in Viral Replication
Journal of virology, v 80(9), pp 4406-4414
May 2006
PMID: 16611900
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
The hepatitis B virus (HBV) X protein (HBx) is a multifunctional regulator of cellular signal transduction and transcription pathways and has a critical role in HBV replication. Much of the cytoplasmic signal transduction activity associated with HBx expression and its stimulation of viral replication is attributable to HBx-induced activation of calcium signaling pathways involving Pyk2 and Src tyrosine kinases. To further characterize upstream signal transduction pathways that are required for HBx activity, including activation of Src and mitogen-activated protein kinase (MAPK) cascades, we determined whether focal adhesion kinase (FAK), a known regulator of Src family kinases and the other member of the Pyk2/FAK kinase family, is activated by HBx. We report that HBx activates FAK and that FAK activation is important for multiple HBx functions. Dominant inhibiting forms of FAK blocked HBx activation of Src kinases and downstream signal transduction, HBx stimulation of NF-κB and AP-1-dependent transcription, and HBV DNA replication. We also demonstrate that HBx-induced activation of FAK is dependent on cellular calcium signaling, which is modulated by HBx. Moreover, prolonged expression of HBx increases both FAK activity and its level of expression. FAK activation may play a role in cellular transformation and cancer progression. HBx stimulation of FAK activity and abundance may also be relevant as a potential cofactor in HBV-associated hepatocellular carcinoma.
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Details
- Title
- Activation of Focal Adhesion Kinase by Hepatitis B Virus HBx Protein: Multiple Functions in Viral Replication
- Creators
- Michael J Bouchard - Department of Biochemistry and Molecular Biology, Drexel University College of Medicine, Philadelphia, Pennsylvania 19102Lihua Wang - Department of Biochemistry and Molecular Biology, Drexel University College of Medicine, Philadelphia, Pennsylvania 19102Robert J Schneider - Department of Biochemistry and Molecular Biology, Drexel University College of Medicine, Philadelphia, Pennsylvania 19102
- Publication Details
- Journal of virology, v 80(9), pp 4406-4414
- Publisher
- American Society for Microbiology
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Biochemistry and Molecular Biology
- Web of Science ID
- WOS:000236980000021
- Scopus ID
- 2-s2.0-33646193810
- Other Identifier
- 991014877697504721
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- Collaboration types
- Domestic collaboration
- Web of Science research areas
- Virology