Phosphocysteine in the PRL-CNNM pathway mediates magnesium homeostasis.

ABSTRACT: PRLs (phosphatases of regenerating liver) are frequently overexpressed in human cancers and are prognostic markers of poor survival. Despite their potential as therapeutic targets, their mechanism of action is not understood in part due to their weak enzymatic activity. Previous studies revealed that PRLs interact with CNNM ion transporters and prevent CNNM4-dependent Mg²⁺ transport, which is important for energy metabolism and tumor progression. Here, we report that PRL-CNNM complex formation is regulated by the formation of phosphocysteine. We show that cysteine in the PRL catalytic site is endogenously phosphorylated as part of the catalytic cycle and that phosphocysteine levels change in response to Mg²⁺ levels. Phosphorylation blocks PRL binding to CNNM Mg²⁺

SUBMITTER: Gulerez I 

PROVIDER: S-EPMC5283600 | biostudies-literature | 2016 Dec

REPOSITORIES: biostudies-literature