Protein kinase C regulates nutrient uptake and growth in hepatoma cells
Protein kinase C regulates nutrient uptake and growth in hepatoma cells
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DOI：
10.1067/msy.1998.90568
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发表时间：
1998-08-01
期刊：
影响因子：
3.8
通讯作者：
Souba, WW
中科院分区：
文献类型：
--
作者：
Bode, BP;Reuter, N;Souba, WW
Background. Human hepatoma cells extract glutamine at rates severalfold greater than normal hepatocytes through a high-affinity transporter encoded by the ATB(0) gene, which contains two putative phosphorylation sites for protein kinase C (PKC). The studies presented here were undertaken to determine whether Sq stem B-0-mediated glutamine uptake regulates hepatoma growth and whether PKC regulates the activity of this transporter.Methods. SK-Hep cells were treated with the PKC activator phorbol 12-myristate 13-acetate (PMA) and the initial-rate transport of glutamine and other nutrients measured at specific times thereafter. Growth rates were monitored during culture +/- PMA or an excess of system B-0 substrates relative to glutamine.Results. PMA treatment exerted a rapid (half-life similar to 15 minutes) concentration-dependent inhibition of glutamine uptake rates to 50% of control values via a posttranslational mechanism that decreased transporter maximum velocity. This effect persisted after 24 hours and was abrogated by the PKC inhibitor staurosporine. PMA also significantly decreased amino acid transport System y(+) and System L, activities but not System A. Chronic treatment with PMA (PKC depletion) inhibited SK-Hep growth, as did attenuation of System B-0-mediated! glutamine uptake with other. B-0 substrates.Conclusions, System B-0-mediated glutamine uptake regulates hepatoma cell growth, whereas PKC influences both processes.
