Identification of protein tyrosine phosphatase receptor gamma extracellular domain (sPTPRG) as a natural soluble protein in plasma

PLoS One. 2015 Mar 16;10(3):e0119110. doi: 10.1371/journal.pone.0119110. eCollection 2015.

Abstract

Background: PTPRG is a widely expressed protein tyrosine phosphatase present in various isoforms. Peptides from its extracellular domain have been detected in plasma by proteomic techniques. We aim at characterizing the plasmatic PTPRG (sPTPRG) form and to identify its source.

Methodology/principal findings: The expression of sPTPRG was evaluated in human plasma and murine plasma and tissues by immunoprecipitation and Western blotting. The polypeptides identified have an apparent Mr of about 120 kDa (major band) and 90 kDa (minor band) respectively. Full length PTPRG was identified in the 100.000×g pelleted plasma fraction, suggesting that it was present associated to cell-derived vesicles (exosomes). The release of sPTPRG by HepG2 human hepatocellular carcinoma cell line was induced by ethanol and sensitive to metalloproteinase and not to Furin inhibitors. Finally, increased levels of the plasmatic ∼120 kDa isoform were associated with the occurrence of liver damage.

Conclusions: These results demonstrate that sPTPRG represent a novel candidate protein biomarker in plasma whose increased expression is associated to hepatocyte damage. This observation could open a new avenue of investigation in this challenging field.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Biomarkers / blood
  • Ethanol / pharmacology
  • Exosomes / metabolism
  • Hep G2 Cells
  • Hepatocytes / metabolism*
  • Hepatocytes / pathology*
  • Humans
  • Male
  • Mice
  • Protein Isoforms / blood
  • Proteome
  • Receptor-Like Protein Tyrosine Phosphatases, Class 5 / blood*
  • Receptor-Like Protein Tyrosine Phosphatases, Class 5 / chemistry*

Substances

  • Biomarkers
  • Protein Isoforms
  • Proteome
  • Ethanol
  • PTPRG protein, human
  • Ptprg protein, mouse
  • Receptor-Like Protein Tyrosine Phosphatases, Class 5

Grants and funding

The authors were supported by Associazione Italiana per la Ricerca sul Cancro (Investigator grant: AIRC-IG 4667 issued to CS) and and NPRP grant 4-157-3-052 from the Qatar National Research Fund (a member of the Qatar Foundation). The statements made herein are solely the responsibility of the author(s). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.