The role of zinc transporters in cellular zinc signalling. (360G-Wellcome-091991_Z_10_Z)

Zinc is essential to cells and is transported across cell membranes by zinc transporters which are increasingly aberrantly expressed in a variety of diseases such as diabetes, neurodegeneration and cancer. The discovery of zinc as a second messenger signalling molecule is relatively new and we have further described zinc transporter ZIP7 as the hub of the intracellular zinc signalling pathway due to its location on the endoplasmic reticulum membrane and its ability to release zinc from these sto res into the cytoplasm. It is this zinc release from stores that is responsible for the ability of zinc to inhibit phosphatases in cells and having implications for activation of signalling pathways controlled by tyrosine kinases and others. Excitingly, I have now discovered that ZIP7 requires phosphorylation by Casein Kinase 2 before it can transport zinc, an unprecendented observation for zinc transporters which now needs further detailed examination to discover (1) the extent of the mechanis m, (2) whether it holds for all cell types and (3) whether it is true for other zinc transporters as well. This will have implications for treatment of certain diseases such as cancer as Casein Kinase 2 inhibitors have also been well tolerated in the clinic.