Effects of protein tyrosine phosphatase-PEST are reversed by Akt in T cells

2014 ◽  
Vol 26 (12) ◽  
pp. 2721-2729 ◽  
Author(s):  
Yutaka Arimura ◽  
Kazuhiko Shimizu ◽  
Madoka Koyanagi ◽  
Junji Yagi
Keyword(s):  
T Cells ◽  
Protein Tyrosine Phosphatase ◽  
Tyrosine Phosphatase ◽  
Protein Tyrosine

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.

scholarly journals Stat6 and IRS-2 Cooperate in Interleukin 4 (IL-4)-Induced Proliferation and Differentiation but Are Dispensable for IL-4-Dependent Rescue from Apoptosis

2002 ◽  
Vol 22 (1) ◽  
pp. 117-126 ◽  
Author(s):  
Andrea L. Wurster ◽  
Dominic J. Withers ◽  
Tohru Uchida ◽  
Morris F. White ◽  
Michael J. Grusby
Keyword(s):  
T Cells ◽  
Signaling Pathway ◽  
Protein Tyrosine Phosphatase ◽  
Tyrosine Phosphatase ◽  
Interleukin 4 ◽  
Signaling Proteins ◽  
Protein Tyrosine ◽  
Antiapoptotic Effect ◽  
Induced Changes

ABSTRACT Stat6 and IRS-2 are two important signaling proteins that associate with the cytoplasmic tail of the interleukin 4 (IL-4) receptor. Data from numerous in vitro experiments have led to a model for IL-4 signal transduction in which the Stat6 signaling pathway is responsible for the IL-4 induced changes in gene expression and differentiation events, while the IRS-2 signaling pathway provides mitogenic and antiapoptotic signals. In order to determine the relative contributions of these signaling molecules in primary lymphocytes, we have examined IL-4 responses in T cells from mice deficient for either Stat6 or IRS-2 as well as from mice doubly deficient for both genes. Both IRS-2 and, especially, Stat6 are shown to be critically involved in IL-4-induced proliferation of T cells, presumably through the cooperative regulation of the Cdk inhibitor p27kip1. Like Stat6-deficient Th cells, IRS-2-deficient cells are also compromised in their ability to secrete Th2 cytokines, revealing a previously unrecognized role for IRS-2 in Th2 cell development. Although Stat6 and/or IRS-2 expression is required for IL-4-induced proliferative and differentiative responses, both signaling proteins are dispensable for the antiapoptotic effect of IL-4. However, treatment of lymphocytes with a protein tyrosine phosphatase inhibitor is able to block the antiapoptotic effect of IL-4 specifically in Stat6- or IRS-2-deficient cells and not in wild-type cells. Our results suggest that Stat6 and IRS-2 cooperate in promoting both IL-4-induced proliferative and differentiating responses, while an additional signaling mediator that depends on protein tyrosine phosphatase activity contributes to the antiapoptotic activities of IL-4 in primary T cells.

scholarly journals Regulatory Functions of Protein Tyrosine Phosphatase Receptor Type O in Immune Cells

2021 ◽  
Vol 12 ◽  
Author(s):  
Feiling Xie ◽  
Hongmei Dong ◽  
Hao Zhang
Keyword(s):  
T Cells ◽  
B Cells ◽  
Immune Cells ◽  
Protein Tyrosine Phosphatase ◽  
Molecular Mechanisms ◽  
Tyrosine Phosphatase ◽  
Protein Tyrosine Phosphatases ◽  
Receptor Type ◽  
Protein Tyrosine ◽  
Cellular Processes

The members of the protein tyrosine phosphatase (PTP) family are key regulators in multiple signal transduction pathways and therefore they play important roles in many cellular processes, including immune response. As a member of PTP family, protein tyrosine phosphatase receptor type O (PTPRO) belongs to the R3 receptor-like protein tyrosine phosphatases. The expression of PTPRO isoforms is tissue-specific and the truncated PTPRO (PTPROt) is mainly observed in hematopoietic cells, including B cells, T cells, macrophages and other immune cells. Therefore, PTPROt may play an important role in immune cells by affecting their growth, differentiation, activation and immune responses. In this review, we will focus on the regulatory roles and underlying molecular mechanisms of PTPRO/PTPROt in immune cells, including B cells, T cells, and macrophages.

IL-6 influences PD-L1 expression in monocytes and macrophages by effecting protein tyrosine phosphatase receptor type O expression in-human breast cancer.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e15570-e15570
Author(s):  
Lin Chen ◽  
Jinhai Tang
Keyword(s):  
Breast Cancer ◽  
T Cells ◽  
Protein Tyrosine Phosphatase ◽  
Human Breast Cancer ◽  
Tyrosine Phosphatase ◽  
Receptor Type ◽  
Human Breast ◽  
Protein Tyrosine ◽  
Monocytes And Macrophages

e15570 Background: We 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 breast cancer (BC). Methods: The expression and correlation of all the indices were explored in monocytes and tumor infiltrating macrophages within both human and mice BC. The mechanic regulations were studied by using both in vitro and in vivo studies. Results: We found a significant decrease in PTPRO in BC peripheral monocytes that was associated with increased PD-L1 expression in peripheral monocytes and tumor-associated macrophages (TAMs) in BC. Monocyte PD-L1 and PTPRO therefore could serve as valuable prognostic indicators for post-surgery patients with BC 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-25-3p axis. Monocytes and TAMs showed significantly increased miR-25-3p expression, which could target the 3' untranslated region of PTPRO. The miR-25-3p expression positively correlated with serum IL-6 levels, but inversely correlated with PTPRO in BC monocytes. IL-6/STAT3/c-MYC activation enhanced in vitro miR-25-3p transcription and decreased PTPRO, while further promoting PD-L1 secretion. Adoptive cell transfer of c-MYC/miR-25-3p–modified monocytes promoted tumor growth by downregulating PTPRO and causing a PD-L1–induced immunosuppression in breast tumor model. Conclusions: Increased serum IL-6 downregulated PTPRO expression in BC monocytes and macrophages by activating STAT3/c-MYC/miR-25-3p and by further enhancing PD-L1 expression through JAK2/STAT1 and JAK2/STAT3/c-MYC signaling.

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