Hepatitis B virus X protein activates a survival signaling by linking Src to phosphatidylinositol 3-kinase
Journal
Journal of Biological Chemistry
Journal Volume
278
Journal Issue
34
Pages
31807-31813
Date Issued
2003
Author(s)
Abstract
We have previously shown that transactivation-proficient hepatitis virus B X protein (HBx) protects Hep 3B cells from transforming growth factor-β (TGF-β-induced apoptosis via activation of the phosphatidylinositol 3-kinase (PI 3-kinase)/Akt signaling pathway. This work further investigated how HBx activates PI 3-kinase. Src activity was elevated in Hep 3B cells following expression of transactivation-proficient HBx or HBx-GFP fusion proteins. The Src family kinase inhibitor PP2 and C-terminal Src kinase (Csk) both alleviated HBx-mediated PI 3-kinase activation and protection from TGF-β-induced apoptosis. Therefore, HBx activated a survival signal by linking Src to PI 3-kinase. Systemic subcellular fractionation and membrane flotation assays indicated that ?1.5% of ectopically expressed HBxGFP was associated with periplasmic membrane where Src was located. However, neither nucleus-targeted nor periplasmic membrane-targeted HBxGFP was able to upregulate Src activity or to augment PI 3-kinase survival signaling pathway.
SDGs
Other Subjects
Bioassay; Biological membranes; Cell culture; Chemical activation; Proteins; Signaling pathways; Viruses; green fluorescent protein; hepatitis b virus x protein; hybrid protein; phosphatidylinositol 3 kinase; protein kinase B; protein kinase p60; transforming growth factor beta; unclassified drug; virus protein; animal cell; apoptosis; article; carboxy terminal sequence; cell fractionation; cell membrane; cell protection; controlled study; cytoplasm; enzyme activation; enzyme binding; enzyme inhibition; flotation; Hepatitis B virus; nonhuman; priority journal; protein analysis; protein expression; protein targeting; signal transduction; survival; transactivation; 1-Phosphatidylinositol 3-Kinase; Amino Acid Sequence; Base Sequence; Cell Line; DNA Primers; Molecular Sequence Data; Protein Binding; Signal Transduction; src-Family Kinases; Trans-Activators; Animalia; Hepatitis B virus; RNA viruses
Type
journal article