scholarly journals CD45 and RPTPα display different protein tyrosine phosphatase activities in T lymphocytes

1997 ◽  
Vol 327 (3) ◽  
pp. 867-876 ◽  
Author(s):  
H. W. David NG ◽  
D. Mojgan JABALI ◽  
Arpita MAITI ◽  
Peter BORODCHAK ◽  
W. Kenneth HARDER ◽  
...  
Keyword(s):  
T Cells ◽  
Tyrosine Phosphatase ◽  
Protein Tyrosine Phosphatases ◽  
Cell Receptor ◽  
Artificial Substrates ◽  
Receptor Protein ◽  
Tyrosine Phosphatases ◽  
Recombinant Enzymes ◽  
Protein Tyrosine

To examine the substrate specificity and function of two receptor protein tyrosine phosphatases, CD45 and RPTPα, RPTPα was expressed in a CD45-, T-cell receptor (TCR)+, BW5147 T-lymphoma cell. High levels of expression of RPTPα did not fully restore either proximal or distal TCR-mediated signalling events. RPTPα was unable to reconstitute the phosphorylation of CD3ζ and did not increase the expression of the activation marker, CD69, on stimulation with TCR/CD3. RPTPα did not significantly alter the phosphorylation state or kinase activity of two CD45 substrates, p56lck or p59fyn, suggesting that RPTPα does not have the same specificity or function as CD45 in T-cells. Further comparison of the two phosphatases indicated that immunoprecipitated RPTPα was approx. one-seventh to one-tenth as active as CD45 when tested against artificial substrates. This difference in activity was also observed in vitro with purified recombinant enzymes at physiological pH. Additional analysis with Src family phosphopeptides and recombinant p56lck as substrates indicated that CD45 was consistently more active than RPTPα, having both higher Vmax and lower Km values. Thus CD45 is intrinsically a much more active phosphatase than RPTPα, which provides one reason why RPTPα cannot effectively dephosphorylate p56lck and substitute for CD45 in T-cells. This work establishes that these two related protein tyrosine phosphatases are not interchangeable in T-cells and that this is due, at least in part, to quantitative differences in phosphatase activity.

scholarly journals No Obvious Abnormality in Mice Deficient in Receptor Protein Tyrosine Phosphatase β

2000 ◽  
Vol 20 (20) ◽  
pp. 7706-7715 ◽  
Author(s):  
S. Harroch ◽  
M. Palmeri ◽  
J. Rosenbluth ◽  
A. Custer ◽  
M. Okigaki ◽  
...  
Keyword(s):  
Nervous System ◽  
Neurite Outgrowth ◽  
Tyrosine Phosphatase ◽  
Protein Tyrosine Phosphatases ◽  
Structural Features ◽  
Receptor Protein ◽  
Protein Tyrosine ◽  
Deficient Mice

ABSTRACT The development of neurons and glia is governed by a multitude of extracellular signals that control protein tyrosine phosphorylation, a process regulated by the action of protein tyrosine kinases and protein tyrosine phosphatases (PTPs). Receptor PTPβ (RPTPβ; also known as PTPζ) is expressed predominantly in the nervous system and exhibits structural features common to cell adhesion proteins, suggesting that this phosphatase participates in cell-cell communication. It has been proposed that the three isoforms of RPTPβ play a role in regulation of neuronal migration, neurite outgrowth, and gliogenesis. To investigate the biological functions of this PTP, we have generated mice deficient in RPTPβ. RPTPβ-deficient mice are viable, are fertile, and showed no gross anatomical alterations in the nervous system or other organs. In contrast to results of in vitro experiments, our study demonstrates that RPTPβ is not essential for neurite outgrowth and node formation in mice. The ultrastructure of nerves of the central nervous system in RPTPβ-deficient mice suggests a fragility of myelin. However, conduction velocity was not altered in RPTPβ-deficient mice. The normal development of neurons and glia in RPTPβ-deficient mice demonstrates that RPTPβ function is not necessary for these processes in vivo or that loss of RPTPβ can be compensated for by other PTPs expressed in the nervous system.

scholarly journals In Vitro Characterization of the Bacillus subtilis Protein Tyrosine Phosphatase YwqE

2005 ◽  
Vol 187 (10) ◽  
pp. 3384-3390 ◽  
Author(s):  
Ivan Mijakovic ◽  
Lucia Musumeci ◽  
Lutz Tautz ◽  
Dina Petranovic ◽  
Robert A. Edwards ◽  
...  
Keyword(s):  
Bacillus Subtilis ◽  
Tyrosine Phosphatase ◽  
Protein Tyrosine Phosphatases ◽  
Class Ii ◽  
Gram Positive ◽  
Protein Tyrosine ◽  
Gram Positive Bacteria ◽  
New Family ◽  
In Vitro Characterization

ABSTRACT Both gram-negative and gram-positive bacteria possess protein tyrosine phosphatases (PTPs) with a catalytic Cys residue. In addition, many gram-positive bacteria have acquired a new family of PTPs, whose first characterized member was CpsB from Streptococcus pneumoniae. Bacillus subtilis contains one such CpsB-like PTP, YwqE, in addition to two class II Cys-based PTPs, YwlE and YfkJ. The substrates for both YwlE and YfkJ are presently unknown, while YwqE was shown to dephosphorylate two phosphotyrosine-containing proteins implicated in UDP-glucuronate biosynthesis, YwqD and YwqF. In this study, we characterize YwqE, compare the activities of the three B. subtilis PTPs (YwqE, YwlE, and YfkJ), and demonstrate that the two B. subtilis class II PTPs do not dephosphorylate the physiological substrates of YwqE.

scholarly journals Differential Regulation of the Cell Wall Integrity Mitogen-Activated Protein Kinase Pathway in Budding Yeast by the Protein Tyrosine Phosphatases Ptp2 and Ptp3

1999 ◽  
Vol 19 (11) ◽  
pp. 7651-7660 ◽  
Author(s):  
Christopher P. Mattison ◽  
Scott S. Spencer ◽  
Kurt A. Kresge ◽  
Ji Lee ◽  
Irene M. Ota
Keyword(s):  
Cell Wall ◽  
Protein Tyrosine Phosphatases ◽  
Negative Regulator ◽  
Cell Wall Integrity ◽  
Dependent Manner ◽  
Tyrosine Phosphatases ◽  
Protein Tyrosine ◽  
Growth Defects ◽  
Mitogen Activated Protein

ABSTRACT Mitogen-activated protein kinases (MAPKs) are inactivated by dual-specificity and protein tyrosine phosphatases (PTPs) in yeasts. InSaccharomyces cerevisiae, two PTPs, Ptp2 and Ptp3, inactivate the MAPKs, Hog1 and Fus3, with different specificities. To further examine the functions and substrate specificities of Ptp2 and Ptp3, we tested whether they could inactivate a third MAPK, Mpk1, in the cell wall integrity pathway. In vivo and in vitro evidence indicates that both PTPs inactivate Mpk1, but Ptp2 is the more effective negative regulator. Multicopy expression of PTP2, but not PTP3, suppressed growth defects due to the MEK kinase mutation, BCK1-20, and the MEK mutation,MKK1-386, that hyperactivate this pathway. In addition, deletion of PTP2, but not PTP3, exacerbated growth defects due to MKK1-386. Other evidence supported a role for Ptp3 in this pathway. Expression of MKK1-386 was lethal in the ptp2Δ ptp3Δ strain but not in either single PTP deletion strain. In addition, the ptp2Δ ptp3Δ strain showed higher levels of heat stress-induced Mpk1-phosphotyrosine than the wild-type strain or strains lacking either PTP. The PTPs also showed differences in vitro. Ptp2 was more efficient than Ptp3 at binding and dephosphorylating Mpk1. Another factor that may contribute to the greater effectiveness of Ptp2 is its subcellular localization. Ptp2 is predominantly nuclear whereas Ptp3 is cytoplasmic, suggesting that active Mpk1 is present in the nucleus. Last, PTP2 but not PTP3 transcript increased in response to heat shock in a Mpk1-dependent manner, suggesting that Ptp2 acts in a negative feedback loop to inactivate Mpk1.

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 Targeting Tyrosine Phosphatases by 3-Bromopyruvate Overcomes Hyperactivation of Platelets from Gastrointestinal Cancer Patients

2019 ◽  
Vol 8 (7) ◽  
pp. 936 ◽  
Author(s):  
Faria ◽  
Andrade ◽  
Reijm ◽  
Spaander ◽  
de Maat ◽  
...  
Keyword(s):  
Tumor Cell ◽  
Cancer Patients ◽  
Gastrointestinal Cancer ◽  
Molecular Mechanisms ◽  
Tyrosine Phosphatase ◽  
Protein Tyrosine Phosphatases ◽  
Cell Aggregation ◽  
Tyrosine Phosphatases ◽  
Indirect Contact ◽  
Protein Tyrosine

Venous thromboembolism (VTE) is one of the most common causes of cancer related mortality. It has been speculated that hypercoagulation in cancer patients is triggered by direct or indirect contact of platelets with tumor cells, however the underlying molecular mechanisms involved are currently unknown. Unraveling these mechanisms may provide potential avenues for preventing platelet-tumor cell aggregation. Here, we investigated the role of protein tyrosine phosphatases in the functionality of platelets in both healthy individuals and patients with gastrointestinal cancer, and determined their use as a target to inhibit platelet hyperactivity. This is the first study to demonstrate that platelet agonists selectively activate low molecular weight protein tyrosine phosphatase (LMWPTP) and PTP1B, resulting in activation of Src, a tyrosine kinase known to contribute to several platelet functions. Furthermore, we demonstrate that these phosphatases are a target for 3-bromopyruvate (3-BP), a lactic acid analog currently investigated for its use in the treatment of various metabolic tumors. Our data indicate that 3-BP reduces Src activity, platelet aggregation, expression of platelet activation makers and platelet-tumor cell interaction. Thus, in addition to its anti-carcinogenic effects, 3-BP may also be effective in preventing platelet-tumor cell aggregationin cancer patients and therefore may reduce cancer mortality by limiting VTE in patients.

scholarly journals Multiple Functions of the Eya Phosphotyrosine Phosphatase

2015 ◽  
Vol 36 (5) ◽  
pp. 668-677 ◽  
Author(s):  
Ilaria Rebay
Keyword(s):  
Developmental Regulation ◽  
Tyrosine Phosphatase ◽  
Protein Tyrosine Phosphatases ◽  
Transcriptional Coactivator ◽  
Tyrosine Phosphatases ◽  
Phosphotyrosine Phosphatase ◽  
Eyes Absent ◽  
Multiple Functions ◽  
Protein Tyrosine ◽  
Cellular Events

Eyes absent (Eya), a protein conserved from plants to humans and best characterized as a transcriptional coactivator, is also the prototype for a novel class of eukaryotic aspartyl protein tyrosine phosphatases. This minireview discusses recent breakthroughs in elucidating the substrates and cellular events regulated by Eya's tyrosine phosphatase function and highlights some of the complexities, new questions, and surprises that have emerged from efforts to understand how Eya's unusual multifunctionality influences developmental regulation and signaling.

scholarly journals Podocyte Protein, Nephrin, Is a Substrate of Protein Tyrosine Phosphatase 1B

2011 ◽  
Vol 2011 ◽  
pp. 1-10 ◽  
Author(s):  
Lamine Aoudjit ◽  
Ruihua Jiang ◽  
Tae Hoon Lee ◽  
Laura A. New ◽  
Nina Jones ◽  
...  
Keyword(s):  
Actin Cytoskeleton ◽  
Tyrosine Phosphorylation ◽  
Tyrosine Phosphatase ◽  
Protein Tyrosine Phosphatases ◽  
Protein Tyrosine Phosphatase 1B ◽  
Tyrosine Phosphatases ◽  
Puromycin Aminonucleoside ◽  
Protein Tyrosine ◽  
Aminonucleoside Nephrosis ◽  
Puromycin Aminonucleoside Nephrosis

Glomerular podocytes are critical for the barrier function of the glomerulus in the kidney and their dysfunction causes protein leakage into the urine (proteinuria). Nephrin is a key podocyte protein, which regulates the actin cytoskeleton via tyrosine phosphorylation of its cytoplasmic domain. Here we report that two protein tyrosine phosphatases, PTP1B and PTP-PEST negatively regulate nephrin tyrosine phosphorylation. PTP1B directly binds to and dephosphorylates nephrin, while the action of PTP-PEST is indirect. The two phosphatases are also upregulated in the glomerulus in the rat model of puromycin aminonucleoside nephrosis. Both overexpression and inhibition of PTP1B deranged the actin cytoskeleton in cultured mouse podocytes. Thus, protein tyrosine phosphatases may affect podocyte function via regulating nephrin tyrosine phosphorylation.

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