The Journal of Toxicological Sciences
Online ISSN : 1880-3989
Print ISSN : 0388-1350
ISSN-L : 0388-1350
Letter
Activation of EGFR/MEK/ERK/AP-1 signaling mediated by 1,2-naphthoquinone, an atmospheric electrophile, in human pulmonary A549 cells
Chang BeeiNoriko IwamotoTakako InabaYasuhiro ShinkaiYoshito Kumagai
Author information
JOURNALS FREE ACCESS

2013 Volume 38 Issue 5 Pages 793-797

Details
Abstract

1,2-Naphthoquinone (1,2-NQ) is found to be an electrophile contaminated in the atmosphere. Although we found that 1,2-NQ activates epidermal growth factor receptor (EGFR) coupled to inhibition of protein tyrosine phosphatase 1B (PTP1B) activity through covalent modification of Cys121 in human epithelial A431 cells, modulation of its downstream signal transduction pathway caused by 1,2-NQ remains to be elucidated. In the present study, we examined whether 1,2-NQ could affect such cellular signaling in human pulmonary A549 cells. Exposure of A549 cells to 1,2-NQ increased EGFR phosphorylation, resulting in activation of MEK/ERK signaling that was blocked by either PD15035 or PD98059. As a result, DNA binding activity of transcription factor AP-1 was enhanced during exposure to 1,2-NQ in the cells. These results suggest that the atmospheric electrophile phosphorylates EGFR, thereby activating the MEK/ERK/AP-1 signal transduction pathway in A549 cells.

Information related to the author
© 2013 The Japanese Society of Toxicology
Previous article Next article
feedback
Top