期刊
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
卷 279, 期 3, 页码 974-979出版社
ACADEMIC PRESS INC
DOI: 10.1006/bbrc.2000.4044
关键词
PKB/Akt; PI3 kinase; Bad; liver regeneration; apoptosis; growth factors
Liver regeneration is controlled by multiple signaling pathways induced by a variety of growth factors, hormones, and cytokines. Here we report that protein kinase B (PKB)/Akt, part of a key cell survival signaling pathway, is markedly activated after partial hepatectomy (PHX). The antiapoptotic protein Bad, a downstream target of PKB/Akt, is also phosphorylated, This cascade can be activated by various factors in primary hepatocytes, with the strongest activation by insulin and the alpha (1)-adrenergic agonist phenylephrine (PE), followed by IL-6, epidermal growth factor (EGF), and hepatocyte growth factor (HGF). Pretreatment of cells with the specific PI3 kinase inhibitor LY294002 abolished insulin- or PE-activation of PKB/ Akt, suggesting that activation of PKB/Akt is mediated by a PI3 kinase-dependent mechanism. In vivo administration of PE, insulin, IL-6, HGF, or EGF to mice markedly stimulated PKB/Akt in the liver, with the strongest stimulation induced by insulin and PE. Moreover, HGF and insulin were able to attenuate transforming growth factor beta -induced apoptosis in hepatic cells, and these effects were antagonized by LY294002. Taken together, these Findings suggest that rapid activation of PKB/Akt is a key antiapoptotic signaling pathway involved in liver regeneration. (C) 2000 Academic Press.
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