Please use this identifier to cite or link to this item:
Title: EGFR S1166 phosphorylation induced by a combination of EGF and gefitinib has a potentially negative impact on lung cancer cell growth
Authors: Assiddiq, B.F.
Tan, K.Y.
Toy, W. 
Chan, S.P.
Chong, P.K. 
Lim, Y.P. 
Keywords: EGFR
lung cancer
multiple reaction monitoring
Issue Date: 3-Aug-2012
Citation: Assiddiq, B.F., Tan, K.Y., Toy, W., Chan, S.P., Chong, P.K., Lim, Y.P. (2012-08-03). EGFR S1166 phosphorylation induced by a combination of EGF and gefitinib has a potentially negative impact on lung cancer cell growth. Journal of Proteome Research 11 (8) : 4110-4119. ScholarBank@NUS Repository.
Abstract: Phosphorylation of protein plays a key role in the regulation of cellular signal transduction and gene expression. In recent years, targeted mass spectrometry facilitates functional phosphoproteomics by allowing specific protein modifications of target proteins in complex samples to be characterized. In this study, we employed multiple reaction monitoring (MRM) to examine the influence of gefitinib (also known as Iressa) on the phosphorylation sites of EGFR protein before and after EGF treatment. By coupling MRM to MS/MS, 5 phosphotyrosine (Y1110, Y1172, Y1197, Y1069, and Y1092) and 1 S/T (T693) sites were identified on EGFR. Y1197 and T693 were constitutively phosphorylated. All phosphorylation sites were sensitive to gefitinib treatment except T693. Interestingly, gefitinib treatment induced phosphorylation of S1166 only in the presence of EGF. We further showed that lung cancer cells overexpressing phosphomimic S1166D EGFR mutant possessed significantly lower growth and proliferation property compared to wildtype EGFR-expressing cells. While the function and mode of regulation of S1166 remain unclear, our data supports the notion that S1166 represents a regulatory site that exerts a negative regulation on growth and proliferation of cancer cells. The data presented has implication in our understanding of dynamic drug (gefitinib)-target (EGFR) interaction and in improving the efficacy of target-directed therapeutics. © 2012 American Chemical Society.
Source Title: Journal of Proteome Research
ISSN: 15353893
DOI: 10.1021/pr3002029
Appears in Collections:Staff Publications

Show full item record
Files in This Item:
There are no files associated with this item.


checked on Mar 4, 2021


checked on Mar 4, 2021

Page view(s)

checked on Feb 27, 2021

Google ScholarTM



Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.