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 are missing or mutated. Our study using Drosophila is the first to examine overexpressed PRL in genetically controlled animal model. This system confirms that PRL can function as a growth inhibitor under normal and oncogenic conditions that can be dependent on subGDC-0449 Hedgehog inhibitor membrane distribution. SB203580 dPRL-1 is a ubiquitously expressed protein found in both proliferating and differentiated tissues of Drosophila that can function as a growth inhibitor at elevated levels. Our 
work supports the model that other cellular alterations are required for elevated levels of PRL to promote cancer. For example, because the CAAX motif is required for dPRL-1 to suppress growth, cellular modifications that interfere with the motif could be one means towards enabling PRLs to act as oncogenes instead. Indeed, our analysis of endogenous dPRL-1 expression during embryogenesis demonstrated that dPRL-1 levels can be high in the cytoplasm in spite of an intact CAAX motif, suggesting other proteins can override CAAXdriven membrane localization. While others�� work has highlighted the need of the CAAX motif for PRLs function, we are the first to see that at least one member of the PRL family can still associate with the plasma membrane without CAAX. This association may occur through the polybasic region adjacent to CAAX, which has been shown to be required for membrane association in addition to CAAX. Our work is also the first to report the accumulation of a PRL family member to apico-lateral locations in epithelial cells; suggesting that dPRL-1 is forming stable interactions with other membrane-bound proteins. Intriguingly, we found that elevated levels of dPRL-1 can have opposing outcomes in genetic backgrounds expressing known oncogenes; resulting in synergistic lethality with Ras but rescuing Src-induced lethality. Src overexpression likely results in lethality because the massively overgrown wing disc becomes developmentally disorganized. While dPRL-1 effectively inhibits Src-induced overgrowth, another mechanism to counter Src function must exist because dPRL-1NC, which does not inhibit growth under normal levels of Src, retains the ability to counter Src-induced lethality. One possibility was that dPRL-1/dPRL-1NC could increase apoptosis, thus eliminating excess tissue. Furthermore, this phenotype could be accomplished by dPRL-1 leading to an increase in Src activity as has been seen in mammalian studies,,. Previous studies in Drosophila have shown a dose response with lower levels of Src leading to proliferation but higher levels resulting in apoptosis. However, we did not detect elevated levels of apoptosis in animals overexpressing both dPRL-1 and Src.