Physiological and oncogenic roles of the PRL phosphatases

FEBS J. 2018 Nov;285(21):3886-3908. doi: 10.1111/febs.14503. Epub 2018 May 27.


The human Phosphatase of Regenerative Liver (PRL) family comprises three members (PRL-1, -2, -3; gene name PTP4A1, PTP4A2, PTP4A3) that are highly expressed in a majority of cancers. This review summarizes our current understanding of PRL biology, including an overview of their evolutionary relationships and the regulatory mechanisms controlling their expression. We provide an updated view on our current knowledge on the PRL functions in solid tumors, hematological cancer, and normal physiology, particularly emphasizing on the use of in vivo mouse models. We also highlight a novel relationship positioning PRL as a central node controlling magnesium homeostasis through an association with the CNNM proteins, which are involved in magnesium transport.

Keywords: CNNM; PRL phosphatase; PTP4A; cancer; magnesium; phosphatase regenerating liver; physiology; protein tyrosine phosphatase; regulation; signaling.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Cell Cycle Proteins / metabolism
  • Homeostasis*
  • Humans
  • Liver Regeneration*
  • Membrane Proteins / metabolism
  • Neoplasm Proteins / metabolism
  • Neoplasms / enzymology*
  • Neoplasms / pathology*
  • Oncogenes*
  • Protein Tyrosine Phosphatases / metabolism*


  • Cell Cycle Proteins
  • Membrane Proteins
  • Neoplasm Proteins
  • PTP4A1 protein, human
  • PTP4A2 protein, human
  • PTP4A3 protein, human
  • Protein Tyrosine Phosphatases