Histidine domain-protein tyrosine phosphatase interacts with Grb2 and GrpL

PLoS One. 2010 Dec 15;5(12):e14339. doi: 10.1371/journal.pone.0014339.


Background: Histidine domain-protein tyrosine phosphatase (HD-PTP) plays a key role in vesicle trafficking and biogenesis. Although it is a large protein with at least five distinct structural domains, only a few of its interactors are presently known, and the significance of these interactions is largely obscure.

Methodology and results: In this study we performed a yeast two-hybrid screening using a human colon cDNA library and found that Grb2 and GrpL are binding partners of HD-PTP. Co-immunoprecipitation, pull-down and immunocytochemistry experiments confirmed the interactions. We also discovered that the central proline-rich and histidine-rich domain of HD-PTP is responsible for these interactions.

Significance: The interaction of HD-PTP with two adapters of the Grb2 family, essential for numerous signaling pathways, suggests that HD-PTP might be important for signaling through a plethora of receptors.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing / chemistry
  • Adaptor Proteins, Signal Transducing / metabolism*
  • Base Sequence
  • Colon / metabolism
  • GRB2 Adaptor Protein / chemistry
  • GRB2 Adaptor Protein / metabolism*
  • Gene Library
  • HeLa Cells
  • Histidine / chemistry*
  • Humans
  • Molecular Sequence Data
  • Proline / chemistry
  • Protein Binding
  • Protein Structure, Tertiary
  • Protein Tyrosine Phosphatases, Non-Receptor / chemistry*
  • Signal Transduction
  • Two-Hybrid System Techniques


  • Adaptor Proteins, Signal Transducing
  • GRAP2 protein, human
  • GRB2 Adaptor Protein
  • GRB2 protein, human
  • Histidine
  • Proline
  • PTPN23 protein, human
  • Protein Tyrosine Phosphatases, Non-Receptor