Phosphatase Function of PRL-3 Is Insensitive to Divalent Metals In Vitro, ACS Omega (2023)

Phosphatase of regenerating liver 3 (PRL-3) is linked to cancer metastasis and interacts with the cyclin and CBS domain divalent metal cation transport mediator (CNNM) family of proteins to manage the levels of magnesium and other metals within cells. Despite its significance in cancer, the factors that regulate PRL-3’s activity and its interactions with CNNM proteins are not well understood. Our study shows that divalent metal ions like magnesium, calcium, and manganese do not affect PRL-3’s structure, stability, activity, or ability to bind to CNNM proteins. This indicates that PRL-3 does not act as a metal sensor, even though it interacts with CNNM transporters. Laboratory tests revealed that PRL-3 is a broad phosphatase, acting on various molecules like di- and tri-nucleotides, phosphoinositols, and NADPH, but not on other common metabolites. Although metal-binding sites were predicted near PRL-3’s active site, these metals did not change its activity or binding with CNNM. Thus, PRL-3 does not regulate CNNM activity by sensing metals. More research is needed to understand the regulatory mechanisms of PRL-3’s activity and its interactions with CNNM, as this could have therapeutic implications for cancer treatment.

DOI: https://doi.org/10.1021/acsomega.3c04095