Akt phosphorylation on Thr308 but not on Ser473 correlates with Akt protein kinase activity in human non-small cell lung cancer.
Akt phosphorylation on Thr308 but not on Ser473 correlates with Akt protein kinase activity in human non-small cell lung cancer.
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DOI：
10.1038/bjc.2011.132
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发表时间：
2011-05-24
影响因子：
8.8
通讯作者：
Tavare, J. M.
中科院分区：
文献类型：
--
作者：
Vincent, E. E.;Elder, D. J. E.;Thomas, E. C.;Phillips, L.;Morgan, C.;Pawade, J.;Sohail, M.;May, M. T.;Hetzel, M. R.;Tavare, J. M.
蛋白激酶Akt的活性在癌症中经常失调，并且是肿瘤细胞生长和存活的重要因素。Akt活化涉及两个残基的磷酸化：活化环中的苏氨酸308（Thr 308）和C-末端疏水基序中的丝氨酸473（Ser 473）。Ser 473的磷酸化已经在肿瘤样品中作为Akt活性的相关性被广泛研究，但是Thr 308或下游Akt底物的磷酸化很少被评估。将Thr 308和Ser 473的磷酸化状态与三种单独的Akt底物-PRAS 40、TSC 2和TBC 1D 4-在早期人类非小细胞肺癌（NSCLC）的新鲜冷冻样品中的磷酸化状态进行比较。Akt Thr 308磷酸化与每个Akt底物的磷酸化相关，而Akt Ser 473磷酸化与任何底物的磷酸化无关。Thr 308的磷酸化是比Ser 473更可靠的肿瘤样品中Akt蛋白激酶活性的生物标志物。因此，对肿瘤样品中Akt磷酸化或活性与疾病的预测或预后之间的联系的任何评价都应该集中于测量Akt在Thr 308和/或至少一种下游Akt底物上的磷酸化，而不是单独的Akt Ser 473磷酸化。
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. 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). 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. 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.
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