A consensus tyrosine phosphatase domain and a C-terminal prenylation CAAX motify. Only two proteins have been shown to be directly dephosphorylated by PRL: Ezrin and a poorly characterized basic leucine zipper protein called ATF-7. However, in all cases examined, a catalytically active phosphatase domain was required for phenotypes resulting from PRL-3 overexpression, including increases in proliferation, 726169-73-9 migration,, and metastases formation in animal models. Another important regulator of PRL function is farnesylation of the CAAX motif. Either mutating the motif or adding a farnesyltransferase inhibitor leads to subMCE Chemical Bromopyruvic acid cellular redistribution of PRLs, from membrane to nucleus,. This relocalization results in a block to cellular responses to ectopic PRL expression, such as enhanced proliferation, migration,, and metastasis. However, another group determined that cytoplasmic localization is positively related to metastasis of cervical cancer, confounding a direct relationship between PRL subcellular localization and cellular outcome. Two signal transduction pathways that have been implicated as oncogenic effectors of PRLs are Src and PI3K signaling. PRL-3 activates Src signaling,, by reducing the synthesis of protein, Csk, an inhibitor of the pathway, and upregulation of PRL1 activates the Src kinase through increased Tyr416 phosphorylation and cell migration. Similar to its effect on Src signaling, PRL-3 promotes PI3K signaling by reducing levels of a protein that normally antagonizes the pathway, in this case, PTEN. This results in activation of Akt, which is well established as protecting cells against apoptosis and also promoting cell migration,. Interestingly, inhibition of Akt has also been shown to be a key player for PRL-3 to arrest cells. Experimenting with levels of PRL-3 overexpression appears to reconcile the opposing effects of PRL-3 on Akt; Basak et al., could detect activation of Akt in response to PRL-3, but only transiently, until level of PRL-3 became highly elevated. Although there is a rapidly growing amount of literature on the mammalian family of PRL phosphatases, several studies have conflicting results. These studies each examine PRL in a different genetic environment, which may mean modulators and effectors of PRL localization or function
