Subcellular localization of intracellular protein tyrosine phosphatases in T cells

Gjörloff-Wingren, Anette; Saxena, Manju; Han, Sangyoon J.; Wang, Xiaodong; Alonso, Andrés; Renedo, Marta; Oh, Phil; Williams, Scott; Schnitzer, Jan E.; Mustelin, Tomas

doi:10.1002/1521-4141(2000)30:8<2412::aid-immu2412>3.0.co;2-j

Cited by 116 publications

(113 citation statements)

References 28 publications

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“…Human LYP, PTPH1, SHP1, LMPTP-B and HePTP cDNA in mammalian expression vector pEF5HA were described previously (Bottini et al, 2002;Brockdorff et al, 1999;Gjörloff-Wingren et al, 2000;Saxena et al, 1998;Vang et al, 2005). The HD-PTP cDNA was a gift from Dr. M. Ouchida (Okayama University, Japan; Toyooka et al, 2000) …”

Section: Expression Plasmidsmentioning

confidence: 99%

“…Immunofluorescence staining was performed as before (Gjörloff-Wingren et al, 2000;Nika et al, 2006) and the cells viewed under a Radiance 2100 MP (Bio-Rad, Hercules, CA) confocal laser scanning microscope. A differential interference contrast image was also taken of each cell.…”

Section: Confocal Microscopymentioning

confidence: 99%

“…In addition, even high levels of overexpression of several PTPs (e.g. TCPTP or PTP-MEG2) have no effect at all on TCR signaling (Gjörloff-Wingren et al, 2000).…”

Section: Introductionmentioning

confidence: 99%

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TCR-induced downregulation of protein tyrosine phosphatase PEST augments secondary T cell responses

Arimura

Vang

Tautz

et al. 2008

Molecular Immunology

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We report that the protein tyrosine phosphatase PTP-PEST is expressed in resting human and mouse CD4 + and CD8 + T cells, but not in Jurkat T leukemia cells, and that PTP-PEST protein, but not mRNA, was dramatically down-regulated in CD4 + and CD8 + primary human T cells upon T cell activation. This was also true in mouse CD4 + T cells, but less striking in mouse CD8 + T cells. PTP-PEST reintroduced into Jurkat at levels similar to those in primary human T cells, was a potent inhibitor of TCR-induced transactivation of reporter genes driven by NFAT/AP-1 and NF-κB elements and by the entire IL-2 gene promoter. Introduction of PTP-PEST into previously activated primary human T cells also reduced subsequent IL-2 production by these cells in response to TCR and CD28 stimulation. The inhibitory effect of PTP-PEST was associated with dephosphorylation the Lck kinase at its activation loop site (Y394), reduced early TCR-induced tyrosine phosphorylation, reduced ZAP-70 phosphorylation and inhibition of MAP kinase activation. We propose that PTP-PEST tempers T cell activation by dephosphorylating TCR-proximal signaling molecules, such as Lck, and that down-regulation of PTP-PEST may be a reason for the increased response to TCR triggering of previously activated T cells.

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Section: Expression Plasmidsmentioning

confidence: 99%

Section: Confocal Microscopymentioning

confidence: 99%

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TCR-induced downregulation of protein tyrosine phosphatase PEST augments secondary T cell responses

Arimura

Vang

Tautz

et al. 2008

Molecular Immunology

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“…Strong candidate negative regulators are PTPs, which have the capacity to impede signaling by dephosphorylating positive-regulatory tyrosine residues in different signaling proteins. Of the ϳ65 PTPs that are expressed in T cells, several have thus far been implicated as negative regulators of proximal TCR signaling (11)(12)(13). Included among these is Src homology region 2 domain-containing phosphatase 1 (SHP-1) and PEST-domain phosphatase (PEP) which have been shown to dephosphorylate and inactivate LCK (SHP-1 and PEP) and Zap70 (SHP-1).…”

Section: T Cells Recognize Peptide Fragments Of Foreign Ags Togethermentioning

confidence: 99%

“…PTPN3 comprises an NH 2 -terminal FERM (band 4.1, ezrin, radixin, moesin) domain, a central PDZ (PSD-95, Dlg, ZO-1) domain, and a COOH-terminal PTP domain. Overexpression of PTPN3 in the Jurkat T cell leukemia cell line profoundly inhibits TCR signal transduction leading to activation of the promoter for the T cell growth-promoting cytokine, IL-2 (13,18). Furthermore, a FERM domain-deleted mutant of PTPN3 is impaired in its ability to inhibit TCR-induced IL-2 promoter activity coincident with an inability of this mutant to localize to the plasma membrane (18).…”

Section: T Cells Recognize Peptide Fragments Of Foreign Ags Togethermentioning

confidence: 99%

Normal TCR Signal Transduction in Mice That Lack Catalytically Active PTPN3 Protein Tyrosine Phosphatase

Bauler¹,

Hughes

Arimura

et al. 2007

The Journal of Immunology

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PTPN3 (PTPH1) is a cytoskeletal protein tyrosine phosphatase that has been implicated as a negative regulator of early TCR signal transduction and T cell activation. To determine whether PTPN3 functions as a physiological negative regulator of TCR signaling in primary T cells, we generated gene-trapped and gene-targeted mouse strains that lack expression of catalytically active PTPN3. PTPN3 phosphatase-negative mice were born in expected Mendelian ratios and exhibited normal growth and development. Furthermore, numbers and ratios of T cells in primary and secondary lymphoid organs were unaffected by the PTPN3 mutations and there were no signs of spontaneous T cell activation in the mutant mice with increasing age. TCR-induced signal transduction, cytokine production, and proliferation was normal in PTPN3 phosphatase-negative mice. This was observed using both quiescent T cells and recently stimulated T cells where expression of PTPN3 is substantially up-regulated. We conclude, therefore, that the phosphatase activity of PTPN3 is dispensable for negative regulation of TCR signal transduction and T cell activation.

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Expression of the putative tumor suppressor gene PTPN13/PTPL1 is an independent prognostic marker for overall survival in breast cancer

Révillion

Puech

Rabenoelina

et al. 2008

Intl Journal of Cancer

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Although it is well established that some protein tyrosine kinases have a prognostic value in breast cancer, the involvement of protein tyrosine phosphatases (PTPs) is poorly substantiated for breast tumors. Three of these enzymes (PTP-gamma, LAR, and PTPL1) are already known to be regulated by estrogens or their antagonists in human breast cancer cells. We used a real-time reverse transcriptase polymerase chain reaction method to test the expression levels of PTP-gamma, LAR and its neuronal isoform, and PTPL1 in a training set of RNA from 59 breast tumors. We sought correlations between levels of these molecular markers, current tumor markers, and survival. We then quantified the expression level of the selected phosphatase in 232 additional samples, resulting in a testing set of 291 breast tumor RNAs from patients with a median follow-up of 6.4 years. The Spearman nonparametric test revealed correlations between PTPL1 expression and differentiation markers. Cox univariate analysis of the overall survival studies demonstrated that PTPL1 is a prognostic factor [risk ratio (RR) 5 0.45], together with the progesterone receptor (PR) (RR 5 0.52) and node involvement (RR 5 1.58). In multivariate analyses, PTPL1 and PR retained their prognostic value (RRs of 0.48 and 0.55, respectively). This study demonstrates for the first time that PTPL1 expression level is an independent prognostic indicator of favorable outcome for patients with breast cancer. In conjunction with our mechanistic studies, this finding identifies PTPL1 as an important regulatory element of human breast tumor aggressiveness and sensitivity to treatments such as antiestrogens and antiaromatase.

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Subcellular localization of intracellular protein tyrosine phosphatases in T cells

Cited by 116 publications

References 28 publications

TCR-induced downregulation of protein tyrosine phosphatase PEST augments secondary T cell responses

TCR-induced downregulation of protein tyrosine phosphatase PEST augments secondary T cell responses

Normal TCR Signal Transduction in Mice That Lack Catalytically Active PTPN3 Protein Tyrosine Phosphatase

Expression of the putative tumor suppressor gene PTPN13/PTPL1 is an independent prognostic marker for overall survival in breast cancer

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