scholarly journals Absence of CTLA-4 Lowers the Activation Threshold of Primed CD8+ TCR-Transgenic T Cells: Lack of Correlation with Src Homology Domain 2-Containing Protein Tyrosine Phosphatase

2001 ◽  
Vol 166 (6) ◽  
pp. 3900-3907 ◽  
Author(s):  
Thomas F. Gajewski ◽  
Francesca Fallarino ◽  
Patrick E. Fields ◽  
Fabiola Rivas ◽  
Maria-Luisa Alegre
Keyword(s):  
T Cells ◽  
Protein Tyrosine Phosphatase ◽  
Tyrosine Phosphatase ◽  
Activation Threshold ◽  
Protein Tyrosine ◽  
Src Homology

scholarly journals Hepatitis C Virus Core Protein Down-Regulates Expression of Src-Homology 2 Domain Containing Protein Tyrosine Phosphatase by Modulating Promoter DNA Methylation

Viruses ◽  
2021 ◽  
Vol 13 (12) ◽  
pp. 2514
Author(s):  
Priya Devi ◽  
Seisuke Ota ◽  
Tanel Punga ◽  
Anders Bergqvist
Keyword(s):  
T Cells ◽  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Protein Tyrosine Phosphatase ◽  
Tyrosine Phosphatase ◽  
Cpg Methylation ◽  
Protein Accumulation ◽  
C Protein ◽  
Protein Tyrosine ◽  
Src Homology

Hepatitis C virus (HCV) is the major causative pathogen associated with liver cirrhosis and hepatocellular carcinoma. The main virion component, the core (C) protein, has been implicated in several aspects of HCV pathology including oncogenesis and immune subversion. Here we show that expression of the C protein induced specific tyrosine phosphorylation of the TCR-related signaling proteins ZAP-70, LAT and PLC-γ in the T cells. Stable expression of the C protein specifically reduced Src homology domain 2-containing protein tyrosine phosphatase 1 (SHP-1) mRNA and protein accumulation. Quantitative CpG methylation analysis revealed a distinct CpG methylation pattern at the SHP-1 gene promoter in the C protein expressing cells that included specific hypermethylation of the binding site for Sp1 transcription factor. Collectively, our results suggest that HCV may suppress immune responses and facilitate its own persistence by deregulating phosphotyrosine signaling via repressive epigenetic CpG modification at the SHP-1 promoter in the T cells.

Molecular cloning of a novel protein-tyrosine phosphatase SH-PTP3 with sequence similarity to the src -homology region 2

FEBS Letters ◽  
1992 ◽  
Vol 314 (3) ◽  
pp. 335-339 ◽  
Author(s):  
Masaaki Adachi ◽  
Masuo Sekiya ◽  
Toshiki Miyachi ◽  
Keiki Matsuno ◽  
Yuji Hinoda ◽  
...  
Keyword(s):  
Molecular Cloning ◽  
Protein Tyrosine Phosphatase ◽  
Sequence Similarity ◽  
Tyrosine Phosphatase ◽  
Protein Tyrosine ◽  
Homology Region ◽  
Src Homology ◽  
Novel Protein

scholarly journals IL-6 promotes PD-L1 expression in monocytes and macrophages by decreasing protein tyrosine phosphatase receptor type O expression in human hepatocellular carcinoma

2020 ◽  
Vol 8 (1) ◽  
pp. e000285 ◽  
Author(s):  
Wenjie Zhang ◽  
Yang Liu ◽  
Zhongyi Yan ◽  
Hui Yang ◽  
Wei Sun ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
T Cells ◽  
Protein Tyrosine Phosphatase ◽  
Tyrosine Phosphatase ◽  
Human Hepatocellular Carcinoma ◽  
Receptor Type ◽  
Protein Tyrosine ◽  
Post Surgery ◽  
Monocytes And Macrophages

BackgroundWe have previously discovered a relationship between the low expression of protein tyrosine phosphatase, receptor type O (PTPRO) in tumor-infiltrating T cells and immunosuppression. The aim of the present study was to investigate the relationship between decreased PTPRO and increased programmed death ligand 1 (PD-L1) in both the peripheral monocytes and tumor-infiltrating macrophages of human hepatocellular carcinoma (HCC).MethodsThe expression and correlation of all the indices were explored in monocytes and tumor-infiltrating macrophages within both human and mice HCC. The mechanic regulations were studied by using both in vitro and in vivo studies.ResultsWe found a significant decrease in PTPRO in HCC peripheral monocytes that was associated with increased PD-L1 expression in peripheral monocytes and tumor-associated macrophages (TAMs) in HCC. Monocyte PD-L1 and PTPRO therefore could serve as valuable prognostic indicators for post-surgery patients with HCC and were associated with increased T-cell exhaustion (Tim3+T cells). A depletion of PTPRO promoted PD-L1 secretion in both monocytes and macrophages through the JAK2/STAT1 and JAK2/STAT3/c-MYC pathways. Increased IL-6 expression was associated with activation of JAK2/STAT3/c-MYC and with decreased PTPRO expression through the STAT3/c-MYC/miR-25–3 p axis. Monocytes and TAMs showed significantly increased miR-25–3 p expression, which could target the 3′ untranslated region of PTPRO. The miR-25–3 p expression positively correlated with serum IL-6 levels, but inversely correlated with PTPRO in HCC monocytes. IL-6/STAT3/c-MYC activation enhanced in vitro miR-25–3 p transcription and decreased PTPRO, while further promoting PD-L1 secretion. Adoptive cell transfer of c-MYC/miR-25–3 p–modified monocytes promoted tumor growth by downregulating PTPRO and causing a PD-L1–induced immunosuppression in an orthotopic tumor transplantation model.ConclusionsIncreased serum IL-6 downregulated PTPRO expression in HCC monocytes and macrophages by activating STAT3/c-MYC/miR-25–3 p and by further enhancing PD-L1 expression through JAK2/STAT1 and JAK2/STAT3/c-MYC signaling.

scholarly journals Disruption of Lymphocyte Function and Signaling in CD45–associated Protein–null Mice

1998 ◽  
Vol 187 (11) ◽  
pp. 1863-1870 ◽  
Author(s):  
Akio Matsuda ◽  
Satoshi Motoya ◽  
Shioko Kimura ◽  
Renee McInnis ◽  
Abby L. Maizel ◽  
...  
Keyword(s):  
Signal Transduction ◽  
T Cells ◽  
Protein Tyrosine Phosphatase ◽  
Tyrosine Kinases ◽  
Tyrosine Phosphatase ◽  
Antigen Receptor ◽  
Lymphocyte Function ◽  
Receptor Signaling ◽  
Protein Tyrosine ◽  
Antigen Receptor Signaling

CD45-AP specifically associates with CD45, a protein tyrosine phosphatase essential for lymphocyte differentiation and antigen receptor–mediated signal transduction. CD45 is thought to mediate antigen receptor signaling by dephosphorylating regulatory tyrosine residues on Src family protein tyrosine kinases such as Lck. However, the mechanism for regulating CD45 protein tyrosine phosphatase activity remains unclear. CD45-AP–null mice were created to examine the role of CD45-AP in CD45-mediated signal transduction. T and B lymphocytes showed reduced proliferation in response to antigen receptor stimulation. Both mixed leukocyte reaction and cytotoxic T lymphocyte functions of T cells were also markedly decreased in CD45-AP–null mice. Interestingly, the interaction between CD45 and Lck was significantly reduced in CD45-AP–null T cells, indicating that CD45-AP directly or indirectly mediates the interaction of CD45 with Lck. Our data indicate that CD45-AP is required for normal antigen receptor signaling and function in lymphocytes.

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