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.
Pascaru
Mihaela
M
Department of Enzymology, Institute of Biochemistry, Bucharest, Romania.
Tanase
Carmen
C
Vacaru
Andrei M
AM
Boeti
Patricia
P
Neagu
Elena
E
Popescu
Irinel
I
Szedlacsek
Stefan E
SE
D020816:Amino Acid Motifs; D000818:Animals; D016466:CHO Cells; D019556:COS Cells; D002522:Chlorocebus aethiops; D006224:Cricetinae; D003412:Cricetulus; D005786:Gene Expression Regulation; D006367:HeLa Cells; D006801:Humans; D007700:Kinetics; D008099:Liver / Q000473:pathology; D009154:Mutation; D009363:Neoplasm Proteins / Q000235:genetics* / Q000378:metabolism; D010744:Phosphoric Monoester Hydrolases / Q000378:metabolism; D017434:Protein Structure, Tertiary; D017027:Protein Tyrosine Phosphatases / Q000235:genetics* / Q000378:metabolism; D012038:Regeneration
D009363:Neoplasm Proteins; D010744:Phosphoric Monoester Hydrolases; C484730:PTP4A3 protein, human; D017027:Protein Tyrosine Phosphatases