Characterization of TCR-induced receptor-proximal signaling events negatively regulated by the protein tyrosine phosphatase PEP

Eur J Immunol. 1999 Dec;29(12):3845-54. doi: 10.1002/(SICI)1521-4141(199912)29:12<3845::AID-IMMU3845>3.0.CO;2-U.

Abstract

The proline-, glutamic acid-, serine- and threonine-enriched protein tyrosine phosphatase PEP, which is expressed primarily in hematopoietic cells, was recently discovered to be physically associated with the 50-kDa cytosolic protein tyrosine kinase (PTK) Csk, an important suppressor of Src family PTK, including Lck and Fyn in T cells. We report that this phosphatase has an inhibitory effect on TCR-induced transcriptional activation of the c-fos proto-oncogene and elements from the IL-2 gene promoter. Catalytically inactive mutants of PEP had no effects in these assays. Expression of PEP also reduced activation of the N-terminal c-Jun kinase Jnk2 in response to receptor ligation, but not in response to UV light. In agreement with a more receptor-proximal site of action, we found that PEP reduced the TCR-induced increase in tyrosine phosphorylation of an Lck mutant, Lck-Y505F, which is only phosphorylated on tyrosine 394, the positive regulatory site. Finally, we observed that PEP reduced c-fos activation in a synergistic manner with Csk, supporting the notion that these two enzymes form a functional team acting on Src family kinases involved in TCR signaling.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Humans
  • Jurkat Cells
  • Lymphocyte Activation / immunology
  • Protein Tyrosine Phosphatase, Non-Receptor Type 12
  • Protein Tyrosine Phosphatases / immunology*
  • Receptors, Antigen, T-Cell / immunology*
  • Signal Transduction / immunology*
  • T-Lymphocytes / immunology*

Substances

  • Receptors, Antigen, T-Cell
  • PTPN12 protein, human
  • Protein Tyrosine Phosphatase, Non-Receptor Type 12
  • Protein Tyrosine Phosphatases