Nuclear localization of non-receptor protein tyrosine phosphatase ε is regulated by its unique N-terminal domain

Judith Kraut, Gloria Volohonsky, Hila Toledano-Katchalski, Ari Elson

Research output: Contribution to journalArticlepeer-review

Abstract

Precise subcellular localization is an important factor in regulation of the functions of protein tyrosine phosphatases. The non-receptor form of protein tyrosine phosphatase ε (cyt-PTPε) can be found in cell nuclei, among other cellular locations, while p67 PTPε, a naturally occurring isoform which lacks the 27 N terminal residues of cyt-PTPε, is exclusively cytosolic. Using deletion and scanning mutagenesis we report that the first 10 amino acid residues of cyt-PTPε, 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-PTPε in cell nuclei. Of the four known protein forms of PTPε, cyt-PTPε 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-PTPε is therefore to regulate its subcellular localization. The existence of naturally occurring forms of PTPε which lack this sequence and which are generated by translational and posttranslational mechanisms, suggests that nuclear localization of cyt-PTPε can be actively regulated by cells.

Original languageEnglish
Pages (from-to)182-189
Number of pages8
JournalExperimental Cell Research
Volume281
Issue number2
DOIs
StatePublished - 2002
Externally publishedYes

Bibliographical note

Funding Information:
This study was supported by The Israel Science Foundation, founded by The Israel Academy of Sciences and Humanities. A.E. is an incumbent of the Adolfo and Evelyn Blum Career Development Chair in Cancer Research at the Weizmann Institute of Science.

Keywords

  • Hydrogen peroxide
  • Nuclear localization signal
  • Oxidative stress
  • Tyrosine phosphatase

ASJC Scopus subject areas

  • Cell Biology

Fingerprint

Dive into the research topics of 'Nuclear localization of non-receptor protein tyrosine phosphatase ε is regulated by its unique N-terminal domain'. Together they form a unique fingerprint.

Cite this