PTPH1 Is a Predominant Protein-tyrosine Phosphatase Capable of Interacting with and Dephosphorylating the T Cell Receptor ζ Subunit

Margaret S. Sozio, Meredith A. Mathis, Jennifer A. Young, Sebastien Wälchli, Lisa A. Pitcher, Philip C. Wrage, Beatrix Bartók, Amanda Campbell, Julian D. Watts, Ruedi Aebersold, Rob Hooft Van Huijsduijnen, Nicolai S C Van Oers

Research output: Contribution to journalArticlepeer-review

50 Scopus citations


Protein-tyrosine phosphatases (PTPases) play key roles in regulating tyrosine phosphorylation levels in cells, yet the identity of their substrates remains limited. We report here on the identification of PTPases capable of dephosphorylating the phosphorylated immune tyrosine-based activation motifs present in the T cell receptor ζ subunit. To characterize these PTPases, we purified enzyme activities directed against the phosphorylated T cell receptor ζ subunit by a combination of anion and cation chromatography procedures. A novel ELISA-based PTPase assay was developed to rapidly screen protein fractions for enzyme activity following the various chromatography steps. We present data that SHP-1 and PTPH1 are present in highly enriched protein fractions that exhibit PTPase activities toward a tyrosine-phosphorylated TCR ζ substrate (specific activity ranging from 0.23 to 40 pmol/min/μg). We also used a protein-tyrosine phosphatase substrate-trapping library comprising the catalytic domains of 47 distinct protein-tyrosine phosphatases, representing almost all the tyrosine phosphatases identified in the human genome. PTPH1 was the predominant phosphatase capable of complexing phospho-ζ. Subsequent transfection assays indicated that SHP-1 and PTPH1 are the two principal PTPases capable of regulating the phosphorylation state of the TCR ζ ITAMs, with PTPH1 directly dephosphorylating ζ. This is the first reported demonstration that PTPH1 is a candidate PTPase capable of interacting with and dephosphorylating TCR ζ.

Original languageEnglish (US)
Pages (from-to)7760-7769
Number of pages10
JournalJournal of Biological Chemistry
Issue number9
StatePublished - Feb 27 2004

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology


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