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Bass, Rosemary and Edwards, Dylan R. 
ORCID: https://orcid.org/0000-0002-3292-2064
(2010)
ADAMs and protein disulfide isomerase: the key to regulated cell-surface protein ectodomain shedding?
Biochemical Journal, 428 (3).
e3-e5.
ISSN 0264-6021
Abstract
The ADAM disintegrin metalloproteinases (where ADAM is ‘a disintegrin and metalloproteinase’) are a family of transmembrane cell-surface proteins with essential roles in adhesion and proteolytic processing in all animals. The archetypal family member is ADAM17 {also known as TACE [TNFα (tumour necrosis factor α)-converting enzyme]}, which is involved in processing pro-TNFα and in the activation of ligands for the EGFR [EGF (epidermal growth factor) receptor], as well as cleavage of diverse cell-surface receptors and adhesion molecules. ADAM-mediated shedding is itself influenced via cell signalling pathways. In this issue of the Biochemical Journal, Willems et al. make the observation that phorbol ester activates shedding by ADAM17 by affecting the activity of PDI (protein disulfide isomerase). They propose that PDI maintains ADAM17 in an inactive ‘closed’ state and PMA stimulation generates ROS (reactive oxygen species) and thus an altered redox environment, which in turn inactivates PDI and allows ADAM17 to adopt an ‘open’ active conformation. This activation is accompanied by changes in disulfide bonds in the ADAM17 ectodomain. This is a novel and exciting finding that could help to unlock the actions of ADAM sheddases, as well as a host of other mechanisms that rely upon rapid alterations in protein conformation on the cell surface.
| Item Type: | Article |
|---|---|
| Faculty \ School: | Faculty of Science > School of Biological Sciences |
| UEA Research Groups: | Faculty of Medicine and Health Sciences > Research Groups > Cancer Studies Faculty of Science > Research Groups > Cells and Tissues |
| Depositing User: | Users 2731 not found. |
| Date Deposited: | 07 Feb 2011 10:54 |
| Last Modified: | 22 Apr 2023 00:13 |
| URI: | https://ueaeprints.uea.ac.uk/id/eprint/21025 |
| DOI: | 10.1042/BJ20100568 |
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