Effect of overexpression and nuclear translocation of constitutively active PKB-alpha on cellular survival and proliferation in HepG2 cells

Journal of Cellular Biochemistry
Dhananjay GuptaRamji L Khandelwal

Abstract

Protein kinase B (Akt/PKB) is a key component in the PI 3-kinase mediated cell survival pathway and has oncogenic transformation potential. Although the over-expression of PKB-alpha can prevent cell death following growth factor withdrawal, the long-term effects of stable over-expression of PKB-alpha on cell survival in the absence of growth factors remain to be resolved. In the present study, we generated HepG2 cells with stable expression of active PKB-alpha and compared its characteristics with HepG2 cells. Basal as well as insulin-stimulated levels of Ser(473) and Thr(308) phosphorylation in PKB-alpha transfected HepG2 cells were much higher than HepG2 cells. Constitutive expression of active PKB-alpha enabled HepG2 cells to survive up to 96 h without serum in growth media while HepG2 cells fail to survive after 48 h of serum withdrawal. A strong positive correlation (R(2) = 0.71) between cell proliferation and phosphorylated form of PKB-alpha at Thr(308) was observed along with higher levels of phosphorylated 3'-phosphoinositide-dependent kinase-1 (PDK-1). HepG2 cells with constitutive expression of active PKB-alpha also showed higher levels of phosphorylated p65 subunit of nuclear factor-kappaB (NFkappaB) in comparison wi...Continue Reading

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Citations

Mar 24, 2005·Journal of Cellular and Molecular Medicine·Gang SongShideng Bao
Nov 30, 2006·The Journal of Reproduction and Development·Chunhua MengKazuyoshi Taya
Aug 3, 2006·Proceedings of the National Academy of Sciences of the United States of America·Yasuyuki TsujitaMark A Sussman
Aug 28, 2007·Journal of Cellular Biochemistry·Shailly Varma, Ramji L Khandelwal
Apr 11, 2009·The Journal of Pathology·Anuraag ShrivastavRajendra K Sharma
Nov 30, 2018·Archives of Dermatological Research·Miao Zhang, Xiaoyan Zhang
Jan 24, 2007·Biochimica Et Biophysica Acta·Jolita CiapaiteCasper G Schalkwijk

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