Indiana University-Purdue University Indianapolis (IUPUI) / The addition and removal of phosphate groups is a key regulatory mechanism for many cellular processes. The balance between phosphorylation and dephosphorylation is delicate and must be maintained in order for proper cell functions to be carried out. Protein kinases and phosphatases are the keepers of this balance with kinases adding phosphate groups and phosphatases removing them. As such, mutation and/or altered regulation of these proteins can be the driving factor in disease. Phosphatase of Regenerating Liver (PRL) is a family novel of three dual specificity phosphatases (DSPs) first discovered in the regenerating liver tissue of rats. PRLs have also been shown to act as oncogenes in cell culture and in animal models. However, the physiological substrate and mechanisms of the PRLs are not yet known. Recently, our lab has developed a PRL 2 knockout mouse and found several striking phenotypes all of which correspond to a significant increase in PTEN. We also found that PRL 2 is targetable by small molecular inhibitors that can potentially be used to disrupt tumor growth and spermatogenesis. Furthermore, a PTEN heterozygous mouse model crossed into our PRL 2 knockout line was generated to investigate the relevance of PRL interaction with PTEN in cancer.

<p>  </p> <p>The phosphatases of regenerating liver are a subfamily of protein tyrosine phosphatases that consist of PRL1, PRL2 and PRL3. The overexpression of PRLs promote cell proliferation, migration and invasion and contribute to tumorigenesis and metastasis to aggravate survival outcome. Although there is increasing interest in understanding the implication of these phosphatases in tumor development, currently, limited knowledge is available about their mechanism of action and the efficacy of PRL inhibition in <em>in vivo</em> tumor models, the tumor extrinsic role of PRLs that allow them to impact tumor development, as well as <em>in vivo</em> physiological function of PRLs that could implicate them in diseases other than cancer. The work presented here aims to address these limitations.</p> <p><br></p>