Why and how to investigate the role of protein phosphorylation in ZIP and ZnT zinc transporter activity and regulation
| Autor: | Tine E. Thingholm, Lars Rönnstrand, Paul A. Rosenberg |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
Cell signaling
chemistry.chemical_element Carrier Proteins/metabolism Review Zinc Zinc signaling 03 medical and health sciences Cellular and Molecular Neuroscience Protein phosphorylation 0302 clinical medicine Homeostasis Animals Humans Phosphorylation Cation Transport Proteins Molecular Biology 030304 developmental biology Pharmacology 0303 health sciences Signal Transduction/physiology Chemistry Phosphorylation/physiology Homeostasis/physiology Phosphoproteomics Cation Transport Proteins/metabolism Transporter Cell Biology Cell biology Transport protein Zinc/metabolism ZnT Molecular Medicine Signal transduction Carrier Proteins ZIP 030217 neurology & neurosurgery Signal Transduction |
| Zdroj: | Thingholm, T E, Rönnstrand, L & Rosenberg, P A 2020, ' Why and how to investigate the role of protein phosphorylation in ZIP and ZnT zinc transporter activity and regulation ', Cellular and Molecular Life Sciences, vol. 77, no. 16, pp. 3085-3102 . https://doi.org/10.1007/s00018-020-03473-3 Cellular and Molecular Life Sciences |
| ISSN: | 1420-9071 1420-682X |
| DOI: | 10.1007/s00018-020-03473-3 |
| Popis: | Zinc is required for the regulation of proliferation, metabolism, and cell signaling. It is an intracellular second messenger, and the cellular level of ionic, mobile zinc is strictly controlled by zinc transporters. In mammals, zinc homeostasis is primarily regulated by ZIP and ZnT zinc transporters. The importance of these transporters is underscored by the list of diseases resulting from changes in transporter expression and activity. However, despite numerous structural studies of the transporters revealing both zinc binding sites and motifs important for transporter function, the exact molecular mechanisms regulating ZIP and ZnT activities are still not clear. For example, protein phosphorylation was found to regulate ZIP7 activity resulting in the release of Zn2+ from intracellular stores leading to phosphorylation of tyrosine kinases and activation of signaling pathways. In addition, sequence analyses predict all 24 human zinc transporters to be phosphorylated suggesting that protein phosphorylation is important for regulation of transporter function. This review describes how zinc transporters are implicated in a number of important human diseases. It summarizes the current knowledge regarding ZIP and ZnT transporter structures and points to how protein phosphorylation seems to be important for the regulation of zinc transporter activity. The review addresses the need to investigate the role of protein phosphorylation in zinc transporter function and regulation, and argues for a pressing need to introduce quantitative phosphoproteomics to specifically target zinc transporters and proteins involved in zinc signaling. Finally, different quantitative phosphoproteomic strategies are suggested. |
| Databáze: | OpenAIRE |
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