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HERO ID
8204649
Reference Type
Journal Article
Title
Phosphorylation of zinc channel ZIP7 drives MAPK, PI3K and mTOR growth and proliferation signalling
Author(s)
Nimmanon, T; Ziliotto, S; Morris, S; Flanagan, L; Taylor, KM; ,
Year
2017
Is Peer Reviewed?
1
Journal
Metallomics
ISSN:
1756-5901
EISSN:
1756-591X
Publisher
ROYAL SOC CHEMISTRY
Location
CAMBRIDGE
Page Numbers
471-481
Language
English
PMID
28205653
DOI
10.1039/c6mt00286b
Web of Science Id
WOS:000402049600005
URL
https://academic.oup.com/metallomics/article/9/5/471-481/6013634
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Abstract
Zinc is an essential trace element participating in diverse biological processes. Cellular zinc levels are strictly controlled by two families of transport proteins: ZIP channels (SLC39A) and ZnT transporters (SLC30A). ZIP channels increase cytosolic zinc levels by importing zinc into cells or releasing zinc from intracellular stores such as the ER. Among all the 14 human members of the ZIP family, ZIP7 is a gatekeeper of zinc release from intracellular stores, requiring post-translational activation by phosphorylation on residues S275 and S276, resulting in activation of multiple downstream pathways. Employing site-directed mutagenesis, we investigated the importance of these individual serine residues as well as other predicted phosphorylation sites on ZIP7, showing that all four sites are required for maximal ZIP7 activation. Using phosphor-protein arrays, we also discovered the major signalling pathways that were activated as a direct result of ZIP7-mediated zinc release from intracellular stores. These data reveal the role of ZIP7-mediated zinc release from intracellular stores in driving major pathways, such as MAPK, mTOR and PI3K-AKT, involved in providing cell survival and proliferation and often over activated in cancer.
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