Phosphatase of regenerating liver (PRL) (PRL)

The Phosphatase of Regenerating Liver (PRL) family, comprising PRL-1, PRL-2, and PRL-3 (encoded by PTP4A1, PTP4A2, and PTP4A3), represents a group of C-terminal prenylated dual-specificity phosphatases that play critical roles in promoting oncogenesis and metastasis (PMID: 29330177). These enzymes are frequently overexpressed in a wide variety of human cancers, where they drive cell migration, invasion, and survival by modulating signaling pathways such as PI3K/Akt and MAPK (PMID: 30655523). A key biochemical feature of PRLs is their interaction with CNNM magnesium transporters; by binding to CNNM proteins, PRLs inhibit magnesium efflux, thereby increasing intracellular magnesium levels to support the high metabolic demands of cancer cells (PMID: 28234354). Despite their lack of a deep catalytic pocket, which makes them challenging to target with traditional small molecules, they are considered high-priority therapeutic targets due to their strong correlation with poor clinical prognosis and metastatic progression (PMID: 31434150). Current drug discovery efforts focus on small-molecule inhibitors like pentamidine and novel compounds that disrupt the PRL-CNNM interface to suppress tumor growth (PMID: 25605737).

Other names

Protein tyrosine phosphatase type IVAPTP4APTP-CAAXPRL-1 (PTP4A1)PRL-2 (PTP4A2)PRL-3 (PTP4A3)

Phosphatase inhibition and disruption of the PRL-CNNM (cyclin M) complex to regulate intracellular magnesium levels and oncogenic signaling pathways.