PTPN4 negatively regulates CrkI in human cell lines

Juan Zhou, Bingbing Wan, Jingxuan Shan, Huili Shi, Yanhong Li, Keke Huo

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

PTPN4 is a widely expressed non-receptor protein tyrosine phosphatase. Although its overexpression inhibits cell growth, the proteins with which it interacts to regulate cell growth are unknown. In this study, we identified CrkI as a PTPN4-interacting protein using a yeast two-hybrid, and confirmed this interaction using in vitro GST pull-down and co-immunoprecipitation and co-localization assays. We further determined the interactional regions as the SH3 domain of CrkI and the proline-rich region between amino acids 462 and 468 of PTPN4. Notably, overexpression of PTPN4 inhibits CrkI-mediated proliferation and wound healing of HEK293T cells, while knockdown of PTPN4 by siRNA in Hep3B cells enhances CrkI-mediated cell growth and motility. Moreover, our data show that ectopic expression of PTPN4 reduces the phosphorylation level of CrkI in HEK293T cells. These findings suggest that PTPN4 negatively regulates cell proliferation and motility through dephosphorylation of CrkI.

Original languageEnglish
Pages (from-to)297-314
Number of pages18
JournalCellular and Molecular Biology Letters
Volume18
Issue number2
DOIs
Publication statusPublished - Jun 2013

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Keywords

  • CRK
  • Cell proliferation
  • CrkI
  • PTPMEG
  • PTPN4
  • Protein tyrosine phosphatase
  • Protein-protein interactions
  • Subcellular localization
  • Wound-healing assay
  • Yeast two-hybrid

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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