The protein tyrosine phosphatase PTPN4/PTP-MEG1, an enzyme capable of dephosphorylating the TCR ITAMs and regulating NF-κB, is dispensable for T cell development and/or T cell effector functions

Jennifer A. Young, Amy M. Becker, Jennifer J. Medeiros, Virginia S. Shapiro, Andrew Wang, J. David Farrar, Timothy A. Quill, Rob Hooft van Huijsduijnen, Nicolai S C van Oers

Research output: Contribution to journalArticlepeer-review

17 Scopus citations

Abstract

T cell receptor signaling processes are controlled by the integrated actions of families of protein tyrosine kinases (PTKs) and protein tyrosine phosphatases (PTPases). Several distinct cytosolic protein tyrosine phosphatases have been described that are able to negatively regulate TCR signaling pathways, including SHP-1, SHP-2, PTPH1, and PEP. Using PTPase substrate-trapping mutants and wild type enzymes, we determined that PTPN4/PTP-MEG1, a PTPH1-family member, could complex and dephosphorylate the ITAMs of the TCR ζ subunit. In addition, the substrate-trapping derivative augmented basal and TCR-induced activation of NF-κB in T cells. To characterize the contribution of this PTPase in T cells, we developed PTPN4-deficient mice. T cell development and TCR signaling events were comparable between wild type and PTPN4-deficient animals. The magnitude and duration of TCR-regulated ITAM phosphorylation, as well as overall protein phosphorylation, was unaltered in the absence of PTPN4. Finally, Th1- and Th2-derived cytokines and in vivo immune responses to Listeria monocytogenes were equivalent between wild type and PTPN4-deficient mice. These findings suggest that additional PTPases are involved in controlling ITAM phosphorylations.

Original languageEnglish (US)
Pages (from-to)3756-3766
Number of pages11
JournalMolecular Immunology
Volume45
Issue number14
DOIs
StatePublished - Aug 2008

Keywords

  • Cell differentiation
  • Protein kinases/phosphatases
  • Signal transduction
  • T cells
  • Transgenic/knockout

ASJC Scopus subject areas

  • Immunology
  • Molecular Biology

Fingerprint Dive into the research topics of 'The protein tyrosine phosphatase PTPN4/PTP-MEG1, an enzyme capable of dephosphorylating the TCR ITAMs and regulating NF-κB, is dispensable for T cell development and/or T cell effector functions'. Together they form a unique fingerprint.

Cite this