Nuclear localization of non-receptor protein tyrosine phosphatase epsilon is regulated by its unique N-terminal domain.
Precise subcellular localization is an important factor in regulation of the functions of protein tyrosine phosphatases. The non-receptor form of protein tyrosine phosphatase epsilon (cyt-PTP(epsilon)) can be found in cell nuclei, among other cellular locations, while p67 PTP(epsilon), a naturally occurring isoform which lacks the 27 N terminal residues of cyt-PTP(epsilon), is exclusively cytosolic. Using deletion and scanning mutagenesis we report that the first 10 amino acid residues of cyt-PTP(epsilon), in particular residues R4, K5, and R9, are critical components for its nuclear localization. We also establish that increased oxidative stress enhances accumulation of cyt-PTP(epsilon) in cell nuclei. Of the four known protein forms of PTP(epsilon), cyt-PTP(epsilon) is the only one which includes the extreme N-terminal sequence containing R4, K5, and R9. The role of the unique N terminus of cyt-PTP(epsilon) is therefore to regulate its subcellular localization. The existence of naturally occurring forms of PTP(epsilon) which lack this sequence and which are generated by translational and posttranslational mechanisms, suggests that nuclear localization of cyt-PTP(epsilon) can be actively regulated by cells.
Kraut
Judith
J
Department of Molecular Genetics, Weizmann Institute of Science, Rehovot 76100, Israel.
Volohonsky
Gloria
G
Toledano-Katchalski
Hila
H
Elson
Ari
A
D021581:Active Transport, Cell Nucleus / Q000235:genetics; D000595:Amino Acid Sequence / Q000502:physiology; D000818:Animals; D002451:Cell Compartmentation / Q000502:physiology*; D002467:Cell Nucleus / Q000201:enzymology* / Q000648:ultrastructure; D005057:Eukaryotic Cells / Q000166:cytology / Q000201:enzymology*; D015971:Gene Expression Regulation, Enzymologic / Q000502:physiology; D049452:Green Fluorescent Proteins; D008164:Luminescent Proteins; D051379:Mice; D009154:Mutation / Q000235:genetics; D018384:Oxidative Stress / Q000235:genetics; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D017434:Protein Structure, Tertiary / Q000502:physiology; D017027:Protein Tyrosine Phosphatases / Q000235:genetics / Q000378:metabolism*
D008164:Luminescent Proteins; D020033:Protein Isoforms; D049452:Green Fluorescent Proteins; D017027:Protein Tyrosine Phosphatases