Cytoskeletal protein tyrosine phosphatase PTPH1 reduces T cell antigen receptor signaling.
The subgroup of protein tyrosine phosphatases that contain an N-terminal ezrin-, radixin- and moesin homology (ERM) domain and a C-terminal catalytic domain is represented by three enzymes in Jurkat T cells, PTPH1, PTP-MEG1 and PTP36. These enzymes are located at the cytoplasmic face of the plasma membrane and may be involved in regulation of the membrane cytoskeleton, signal transduction, or both. Here we report that expression of PTPH1 in Jurkat T cells reduced the TCR-induced activation of reporter genes encompassing parts of the IL-2 gene promoter and driven by nuclear factor of activated T cells plus activator protein-1. PTP-MEG1 had a weaker inhibitory effect, while PTP36 had none. The catalytically inactive mutants PTPH1-CS and PTP-MEG1-CS lacked effects on gene transcription. Expression of active PTPH1 also reduced receptor-induced activation of Erk2 MAP kinase, its upstream activator, Mek, and the Jnk kinases. The effect of PTPH1 was reduced by deletion of its N-terminal ERM domain. We suggest that PTPH1 inhibits T cell activation by dephosphorylating membrane-associated targets involved in TCR signaling.
Han
S
S
Laboratory of Signal Transduction, La Jolla Cancer Research Center, The Burnham Institute, La Jolla 92037, USA.
Williams
S
S
Mustelin
T
T
D003599:Cytoskeleton / Q000276:immunology; D006801:Humans; D019169:Jurkat Cells; D054589:Protein Tyrosine Phosphatase, Non-Receptor Type 3; D054590:Protein Tyrosine Phosphatase, Non-Receptor Type 4; D017027:Protein Tyrosine Phosphatases / Q000276:immunology*; D054558:Protein Tyrosine Phosphatases, Non-Receptor; D011948:Receptors, Antigen, T-Cell / Q000276:immunology*; D015398:Signal Transduction / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology* / Q000648:ultrastructure
D011948:Receptors, Antigen, T-Cell; C093261:PTPN14 protein, human; C516656:PTPN3 protein, human; C516658:PTPN4 protein, human; D054589:Protein Tyrosine Phosphatase, Non-Receptor Type 3; D054590:Protein Tyrosine Phosphatase, Non-Receptor Type 4; D017027:Protein Tyrosine Phosphatases; D054558:Protein Tyrosine Phosphatases, Non-Receptor