Hepatitis B virus X protein activates a survival signaling by linking SRC to phosphatidylinositol 3-kinase.
We have previously shown that transactivation-proficient hepatitis virus B X protein (HBx) protects Hep 3B cells from transforming growth factor-beta (TGF-beta)-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-beta-induced apoptosis. Therefore, HBx activated a survival signal by linking Src to PI 3-kinase. Systemic subcellular fractionation and membrane flotation assays indicated that approximately 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.
Shih
Wen-Ling
WL
Graduate Institute of Microbiology, College of Medicine, National Taiwan University, Taipei 10063, Taiwan.
Kuo
Min-Liang
ML
Chuang
Shuang-En
SE
Cheng
Ann-Lii
AL
Doong
Shin-Lian
SL
D000595:Amino Acid Sequence; D001483:Base Sequence; D002460:Cell Line; D017931:DNA Primers; D008969:Molecular Sequence Data; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D011485:Protein Binding; D015398:Signal Transduction; D015534:Trans-Activators / Q000502:physiology*; D054334:Viral Regulatory and Accessory Proteins; D019061:src-Family Kinases / Q000378:metabolism*
D017931:DNA Primers; D019869:Phosphatidylinositol 3-Kinases; D015534:Trans-Activators; D054334:Viral Regulatory and Accessory Proteins; D019061:src-Family Kinases; C057628:hepatitis B virus X protein