Analysis of molecular determinants of PRL‐3

In order to analyse whether a C‐terminal polybasic sequence represents a nuclear localization signal (NLS) we obtained several truncated and mutant forms of protein of regerating liver (PRL)‐3 and evaluated their subcellular localization as compared to the wild‐type form. Our results invalidate the hypothesis that this is an NLS. We also analysed the influence of the C‐ and N‐terminal residues on the phosphatase activity of PRL‐3. Our results provide in vitro evidence that the C‐terminal CAAX motif, besides directing the protein farnesylation, plays an additional regulatory role by inhibiting the catalytic efficiency of PRL‐3. Taking into account the results we obtained, as well as reported data, we propose a hypothetical molecular mechanism for the nucleocytoplasmic localization and transfer of PRL‐3.