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Akt phosphorylation on Thr308 but not on Ser473 correlates with Akt protein kinase activity in human non-small cell lung cancer
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-t...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group
2011
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3111153/ https://www.ncbi.nlm.nih.gov/pubmed/21505451 http://dx.doi.org/10.1038/bjc.2011.132 |
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author | Vincent, E E Elder, D J E Thomas, E C Phillips, L Morgan, C Pawade, J Sohail, M May, M T Hetzel, M R Tavaré, J M |
author_facet | Vincent, E E Elder, D J E Thomas, E C Phillips, L Morgan, C Pawade, J Sohail, M May, M T Hetzel, M R Tavaré, J M |
author_sort | Vincent, E E |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-3111153 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2011 |
publisher | Nature Publishing Group |
record_format | MEDLINE/PubMed |
spelling | pubmed-31111532012-05-24 Akt phosphorylation on Thr308 but not on Ser473 correlates with Akt protein kinase activity in human non-small cell lung cancer Vincent, E E Elder, D J E Thomas, E C Phillips, L Morgan, C Pawade, J Sohail, M May, M T Hetzel, M R Tavaré, J M Br J Cancer Molecular Diagnostics 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. Nature Publishing Group 2011-05-24 2011-04-19 /pmc/articles/PMC3111153/ /pubmed/21505451 http://dx.doi.org/10.1038/bjc.2011.132 Text en Copyright © 2011 Cancer Research UK https://creativecommons.org/licenses/by/4.0/This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material.If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit https://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Molecular Diagnostics Vincent, E E Elder, D J E Thomas, E C Phillips, L Morgan, C Pawade, J Sohail, M May, M T Hetzel, M R Tavaré, J M Akt phosphorylation on Thr308 but not on Ser473 correlates with Akt protein kinase activity in human non-small cell lung cancer |
title | Akt phosphorylation on Thr308 but not on Ser473 correlates with Akt protein kinase activity in human non-small cell lung cancer |
title_full | Akt phosphorylation on Thr308 but not on Ser473 correlates with Akt protein kinase activity in human non-small cell lung cancer |
title_fullStr | Akt phosphorylation on Thr308 but not on Ser473 correlates with Akt protein kinase activity in human non-small cell lung cancer |
title_full_unstemmed | Akt phosphorylation on Thr308 but not on Ser473 correlates with Akt protein kinase activity in human non-small cell lung cancer |
title_short | Akt phosphorylation on Thr308 but not on Ser473 correlates with Akt protein kinase activity in human non-small cell lung cancer |
title_sort | akt phosphorylation on thr308 but not on ser473 correlates with akt protein kinase activity in human non-small cell lung cancer |
topic | Molecular Diagnostics |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3111153/ https://www.ncbi.nlm.nih.gov/pubmed/21505451 http://dx.doi.org/10.1038/bjc.2011.132 |
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