Effects of Activating Mutations on EGFR Cellular Protein Turnover and Amino Acid Recycling Determined Using SILAC Mass Spectrometry
Joint Authors
Greig, Michael J.
Niessen, Sherry
Weinrich, Scott L.
Feng, Jun Li
Shi, Manli
Johnson, Ted O.
Source
International Journal of Cell Biology
Issue
Vol. 2015, Issue 2015 (31 Dec. 2015), pp.1-8, 8 p.
Publisher
Hindawi Publishing Corporation
Publication Date
2015-11-24
Country of Publication
Egypt
No. of Pages
8
Main Subjects
Abstract EN
Rapid mutations of proteins that are targeted in cancer therapy often lead to drug resistance.
Often, the mutation directly affects a drug’s binding site, effectively blocking binding of the drug, but these mutations can have other effects such as changing the protein turnover half-life.
Utilizing SILAC MS, we measured the cellular turnover rates of an important non-small cell lung cancer target, epidermal growth factor receptor (EGFR).
Wild-type (WT) EGFR, EGFR with a single activating mutant (Del 746–750 or L858R), and the drug-resistant double mutant (L858R/T790M) EGFR were analyzed.
In non-small cell lung cancer cell lines, EGFR turnover rates ranged from 28 hours in A431 cells (WT) to 7.5 hours in the PC-9 cells (Del 746–750 mutant).
The measurement of EGFR turnover rate in PC-9 cells dosed with irreversible inhibitors has additional complexity due to inhibitor effects on cell viability and results were reported as a range.
Finally, essential amino acid recycling (K and R) was measured in different cell lines.
The recycling was different in each cell line, but the overall inclusion of the effect of amino acid recycling on calculating EGFR turnover rates resulted in a 10–20% reduction in rates.
American Psychological Association (APA)
Greig, Michael J.& Niessen, Sherry& Weinrich, Scott L.& Feng, Jun Li& Shi, Manli& Johnson, Ted O.. 2015. Effects of Activating Mutations on EGFR Cellular Protein Turnover and Amino Acid Recycling Determined Using SILAC Mass Spectrometry. International Journal of Cell Biology،Vol. 2015, no. 2015, pp.1-8.
https://search.emarefa.net/detail/BIM-1065356
Modern Language Association (MLA)
Greig, Michael J.…[et al.]. Effects of Activating Mutations on EGFR Cellular Protein Turnover and Amino Acid Recycling Determined Using SILAC Mass Spectrometry. International Journal of Cell Biology No. 2015 (2015), pp.1-8.
https://search.emarefa.net/detail/BIM-1065356
American Medical Association (AMA)
Greig, Michael J.& Niessen, Sherry& Weinrich, Scott L.& Feng, Jun Li& Shi, Manli& Johnson, Ted O.. Effects of Activating Mutations on EGFR Cellular Protein Turnover and Amino Acid Recycling Determined Using SILAC Mass Spectrometry. International Journal of Cell Biology. 2015. Vol. 2015, no. 2015, pp.1-8.
https://search.emarefa.net/detail/BIM-1065356
Data Type
Journal Articles
Language
English
Notes
Includes bibliographical references
Record ID
BIM-1065356