Why and how to investigate the role of protein phosphorylation in ZIP and ZnT zinc transporter activity and regulation.

Why and how to investigate the role of protein phosphorylation in ZIP and ZnT zinc transporter activity and regulation.
Cell Mol Life Sci. 2020 Feb 19;:
Authors: Thingholm TE, Rönnstrand L, Rosenberg PA
Abstract
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 transporte...

Source: Cellular and Molecular Life Sciences : CMLS - February 18, 2020 Category: Cytology Authors: Thingholm TE, Rönnstrand L, Rosenberg PA Tags: Cell Mol Life Sci Source Type: research