期刊
BRITISH JOURNAL OF CANCER
卷 104, 期 11, 页码 1755-1761出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/bjc.2011.132
关键词
protein kinase B; Akt; biomarker; tumour; phosphorylation
类别
资金
- Wellcome Trust
- Bristol Friends of Oncology
BACKGROUND: The activity of the protein kinase Akt is frequently dysregulated in cancer and is an important factor in the growth and survival of tumour cells. Akt activation involves the phosphorylation of two residues: threonine 308 (Thr308) in the activation loop and serine 473 (Ser473) in the C-terminal hydrophobic motif. Phosphorylation of Ser473 has been extensively studied in tumour samples as a correlate for Akt activity, yet the phosphorylation of Thr308 or of downstream Akt substrates is rarely assessed. METHODS: The phosphorylation status of Thr308 and Ser473 was compared with that of three separate Akt substrates - PRAS40, TSC2 and TBC1D4 in fresh frozen samples of early-stage human non-small cell lung cancer (NSCLC). RESULTS: Akt Thr308 phosphorylation correlated with the phosphorylation of each Akt substrate tested, whereas Akt Ser473 phosphorylation did not correlate with the phosphorylation of any of the substrates examined. CONCLUSION: The phosphorylation of Thr308 is a more reliable biomarker for the protein kinase activity of Akt in tumour samples than Ser473. Any evaluation of the link between Akt phosphorylation or activity in tumour samples and the prediction or prognosis of disease should, therefore, focus on measuring the phosphorylation of Akt on Thr308 and/or at least one downstream Akt substrate, rather than Akt Ser473 phosphorylation alone. British Journal of Cancer (2011) 104, 1755-1761. doi:10.1038/bjc.2011.132 www.bjcancer.com Published online 19 April 2011 (C) 2011 Cancer Research UK
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据