McClurg, UL, Danjo, K, King, HO et al. (3 more authors) (2015) Epithelial cell ADAM17 activation by Helicobacter pylori: role of ADAM17 C-terminus and Threonine-735 phosphorylation. Microbes and Infection: a journal on infectious agents and host defenses, 17 (3). 205 - 214. ISSN 1769-714X
Abstract
Helicobacter pylori transactivates the epidermal growth factor receptor (EGFR) on gastric epithelial cells via a signalling cascade involving a disintegrin and metalloprotease 17 (ADAM17) cleavage of membrane bound heparin binding-epidermal growth factor (HB-EGF). The effects of H. pylori on ADAM17 C-terminus in epithelial cells have been examined. Total cellular ADAM17 and surface expression of ADAM17 were significantly increased by H. pylori in AGS gastric epithelial cells. These changes were associated with ADAM17 C-terminal phosphorylation at T375 and S791. AGS cells lacking the ADAM17 C-terminal domain induced significantly attenuated cleavage of HB-EGF and were also unable to upregulate HB-EGF and EGFR transcripts to the same extent as cells expressing full length ADAM17. In mitotic unstimulated AGS and ADAM17 over-expressing AGS cells, ADAM17 was highly T735 phosphorylated indicating ADAM17 T735 phosphorylation is modified during the cell cycle. In conclusion, H. pylori induced ADAM17 C-terminal T735 and/or S791 phosphorylation in gastric epithelial cells are likely to be an important trigger inducing ADAM17 activation and shedding of HB-EGF leading to EGFR transactivation. ADAM17 over-expression in gastric cancer represents a potential target for therapeutic intervention.
Metadata
Item Type: | Article |
---|---|
Authors/Creators: |
|
Copyright, Publisher and Additional Information: | © 2014 Institut Pasteur. Published by Elsevier Masson SAS. All rights reserved.This is an author produced version of a paper published in Microbes and Infection. Uploaded in accordance with the publisher's self-archiving policy |
Keywords: | Helicobacter pylori; ADAM 17; Phosphorylation; EGFR; HB-EGF; TNF-α |
Dates: |
|
Institution: | The University of Leeds |
Academic Units: | The University of Leeds > Faculty of Medicine and Health (Leeds) > School of Medicine (Leeds) > Inst of Biomed & Clin Sciences (LIBACS) (Leeds) |
Depositing User: | Symplectic Publications |
Date Deposited: | 21 May 2015 14:57 |
Last Modified: | 08 Feb 2018 22:12 |
Published Version: | http://dx.doi.org/10.1016/j.micinf.2014.11.011 |
Status: | Published |
Publisher: | Elsevier |
Identification Number: | 10.1016/j.micinf.2014.11.011 |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:86300 |