Gupta Nutan, Duggal Shweta, Kumar Ajay, Saquib Najmuddin Mohd, Rao Kanury V S
Immunology Group, International Centre for Genetic Engineering and Biotechnology, Aruna Asaf Ali Marg, New Delhi, 110067, India.
Translational Health Science & Technology Institute, NCR, Biotech Cluster, Faridabad, 121001, India.
BMC Res Notes. 2018 May 2;11(1):270. doi: 10.1186/s13104-018-3364-z.
Signal transduction not only initiates entry into the cell cycle, but also reprograms the cell's metabolism. To control abnormalities in cell proliferation, both the aspects should be taken care of, thus pleiotropic signaling molecules are considered as crucial modulators. Considering this, we investigated the role of AKT1 in central carbon metabolism. The role of AKT1 has already been established in the process of cell cycle, but its contribution to the central carbon metabolism is sparsely studied.
To address this, we combined the metabolomics and proteomics approaches. In accordance to our hypothesis, we found that the AKT1 kinase activity is regulating the levels of acetyl CoA through pyruvate dehydrogenase complex. Further, the decreased levels of acetyl CoA and dependency of acetyl CoA acetyl transferase protein on AKT1 kinase activity was also found to perturb the synthesis rate of palmitic acid which is a representative of fatty acid. This was analyzed in the present study using lipid labeling method through mass spectrometry.
信号转导不仅启动细胞进入细胞周期,还会重新编程细胞的新陈代谢。为了控制细胞增殖异常,这两个方面都应予以关注,因此多效性信号分子被视为关键调节因子。考虑到这一点,我们研究了AKT1在中心碳代谢中的作用。AKT1在细胞周期过程中的作用已经明确,但其对中心碳代谢的贡献研究较少。
为解决这一问题,我们结合了代谢组学和蛋白质组学方法。根据我们的假设,我们发现AKT1激酶活性通过丙酮酸脱氢酶复合物调节乙酰辅酶A的水平。此外,还发现乙酰辅酶A水平的降低以及乙酰辅酶A乙酰转移酶蛋白对AKT1激酶活性的依赖性会扰乱作为脂肪酸代表的棕榈酸的合成速率。本研究通过质谱脂质标记法对此进行了分析。