Dead but not gone: The case for PRL as a pseudophosphatase

Background: Protein phosphorylation and dephosphorylation is an integral component of many cellular signaling pathways and regulatory mechanisms. Phosphatases are enzymes that catalyze the removal of phosphate groups from proteins. The phosphatases of regenerating liver (PRLs) are a family of phosphatases which have been correlated with cancer development and metastasis. However, they appear to have weak phosphatase activity and little is known about their physiological substrates. This review discusses PRL from a structural and functional perspective, including recent findings on its interaction with another family of proteins, cyclin M (CNNM). Methods: Articles were obtained from the scientific literature using databases like PubMed and McGill University’s open access institutional repository. This paper specifically focuses on those articles that provided an overview of phosphatases, PRLs, CNNMs, and structural and functional studies of PRLs and CNNMs. In total, 40 articles were selected for the purpose of this review. Summary: Although PRLs retain many of the structural features of other protein tyrosine phosphatases (PTPs) including the phosphatase catalytic motif and regulation via oxidation, other structural features such as mutation of a conserved serine/threonine residue to alanine in the active site disfavor catalytic activity. Moreover, PRL interaction with CNNM appears to be responsible for its oncogenic potential, yet this inter- action does not appear to require PRL phosphatase activity. Thus, PRL may be best classified as a pseudo-phosphatase, which are phosphatase-like proteins that are structurally similar to phosphatases but have acquired a dominant function that does not require phosphatase activity.