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 Critical Role for Protein Tyrosine Phosphatase SHP-1 in Controlling Infection of Central Nervous System Glia and Demyelination by Theiler's Murine Encephalomyelitis Virus

2002 ◽  
Vol 76 (16) ◽  
pp. 8335-8346 ◽  
Author(s):  
Paul T. Massa ◽  
Stacie L. Ropka ◽  
Sucharita Saha ◽  
Karen L. Fecenko ◽  
Kathryn L. Beuler
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Virus Replication ◽  
Protein Tyrosine Phosphatase ◽  
Tyrosine Phosphatase ◽  
Protein Tyrosine ◽  
Normal Littermate ◽  
Encephalomyelitis Virus ◽  
Deficient Mice

ABSTRACT We previously characterized the expression and function of the protein tyrosine phosphatase SHP-1 in the glia of the central nervous system (CNS). In the present study, we describe the role of SHP-1 in virus infection of glia and virus-induced demyelination in the CNS. For in vivo studies, SHP-1-deficient mice and their normal littermates received an intracerebral inoculation of an attenuated strain of Theiler's murine encephalomyelitis virus (TMEV). At various times after infection, virus replication, TMEV antigen expression, and demyelination were monitored. It was found that the CNS of SHP-1-deficient mice uniquely displayed demyelination and contained substantially higher levels of virus than did that of normal littermate mice. Many infected astrocytes and oligodendrocytes were detected in both brains and spinal cords of SHP-1-deficient but not normal littermate mice, showing that the virus replicated and spread at a much higher rate in the glia of SHP-1-deficient animals. To ascertain whether the lack of SHP-1 in the glia was primarily responsible for these differences, glial samples from these mice were cultured in vitro and infected with TMEV. As in vivo, infected astrocytes and oligodendrocytes of SHP-1-deficient mice were much more numerous and produced more virus than did those of normal littermate mice. These findings indicate that SHP-1 is a critical factor in controlling virus replication in the CNS glia and virus-induced demyelination.

scholarly journals Involvement of the Mitochondrial Protein Tyrosine Phosphatase PTPM1 in the Promotion of Conidiation, Development, and Pathogenicity in Colletotrichum graminicola

2021 ◽  
Vol 11 ◽  
Author(s):  
Shaowei Wang ◽  
Guihua Li ◽  
Yi Wei ◽  
Gang Wang ◽  
Yuejia Dang ◽  
...  
Keyword(s):  
Protein Tyrosine Phosphatase ◽  
Fungal Pathogens ◽  
Tyrosine Phosphatase ◽  
Mitochondrial Protein ◽  
Protein Tyrosine Phosphatases ◽  
Host Cells ◽  
Colletotrichum Graminicola ◽  
Protein Tyrosine

The phosphorylation status of proteins, which is determined by protein tyrosine kinases (PTKs) and protein tyrosine phosphatases (PTPs), governs many cellular actions. In fungal pathogens, phosphorylation-mediated signal transduction has been considered to be one of the most important mechanisms in pathogenicity. Colletotrichum graminicola is an economically important corn pathogen. However, whether phosphorylation is involved in its pathogenicity is unknown. A mitochondrial protein tyrosine phosphatase gene, designated CgPTPM1, was deduced in C. graminicola through the use of bioinformatics and confirmed by enzyme activity assays and observation of its subcellular localization. We then created a CgPTPM1 deletion mutant (ΔCgPTPM1) to analyze its biological function. The results indicated that the loss of CgPTPM1 dramatically affected the formation of conidia and the development and differentiation into appressoria. However, the colony growth and conidial morphology of the ΔCgPTPM1 strains were unaffected. Importantly, the ΔCgPTPM1 mutant strains exhibited an obvious reduction of virulence, and the delayed infected hyphae failed to expand in the host cells. In comparison with the wild-type, ΔCgPTPM1 accumulated a larger amount of H2O2 and was sensitive to exogenous H2O2. Interestingly, the host cells infected by the mutant also exhibited an increased accumulation of H2O2 around the infection sites. Since the expression of the CgHYR1, CgGST1, CgGLR1, CgGSH1 and CgPAP1 genes was upregulated with the H2O2 treatment, our results suggest that the mitochondrial protein tyrosine phosphatase PTPM1 plays an essential role in promoting the pathogenicity of C. graminicola by regulating the excessive in vivo and in vitro production of H2O2.

scholarly journals Functions of the Ectodomain and Cytoplasmic Tyrosine Phosphatase Domains of Receptor Protein Tyrosine Phosphatase Dlar In Vivo

2003 ◽  
Vol 23 (19) ◽  
pp. 6909-6921 ◽  
Author(s):  
Neil X. Krueger ◽  
R. Sreekantha Reddy ◽  
Karl Johnson ◽  
Jack Bateman ◽  
Nancy Kaufmann ◽  
...  
Keyword(s):  
Protein Tyrosine Phosphatase ◽  
Tyrosine Phosphatase ◽  
P Element ◽  
Receptor Protein ◽  
Loss Of Function ◽  
Protein Tyrosine ◽  
Receptor Protein Tyrosine Phosphatase ◽  
Catalytically Active

ABSTRACT The receptor protein tyrosine phosphatase (PTPase) Dlar has an ectodomain consisting of three immunoglobulin (Ig)-like domains and nine fibronectin type III (FnIII) repeats and a cytoplasmic domain consisting of two PTPase domains, membrane-proximal PTP-D1 and C-terminal PTP-D2. A series of mutant Dlar transgenes were introduced into the Drosophila genome via P-element transformation and were then assayed for their capacity to rescue phenotypes caused by homozygous loss-of-function genotypes. The Ig-like domains, but not the FnIII domains, are essential for survival. Conversely, the FnIII domains, but not the Ig-like domains, are required during oogenesis, suggesting that different domains of the Dlar ectodomain are involved in distinct functions during Drosophila development. All detectable PTPase activity maps to PTP-D1 in vitro. The catalytically inactive mutants of Dlar were able to rescue Dlar −/− lethality nearly as efficiently as wild-type Dlar transgenes, while this ability was impaired in the PTP-D2 deletion mutants DlarΔPTP-D2 and Dlarbypass . Dlar-C1929S, in which PTP-D2 has been inactivated, increases the frequency of bypass phenotype observed in Dlar −/− genotypes, but only if PTP-D1 is catalytically active in the transgene. These results indicate multiple roles for PTP-D2, perhaps by acting as a docking domain for downstream elements and as a regulator of PTP-D1.

scholarly journals Transmembrane glycoprotein gp150 is a substrate for receptor tyrosine phosphatase DPTP10D in Drosophila cells.

1997 ◽  
Vol 17 (12) ◽  
pp. 6859-6867 ◽  
Author(s):  
S J Fashena ◽  
K Zinn
Keyword(s):  
Tyrosine Phosphatase ◽  
Protein Tyrosine Phosphatases ◽  
Cytoplasmic Domain ◽  
Receptor Protein ◽  
S2 Cells ◽  
Wild Type ◽  
Downstream Signaling ◽  
Transmembrane Glycoprotein

We have begun to explore the downstream signaling pathways of receptor protein tyrosine phosphatases (RPTPs) that control axon guidance decisions in the Drosophila central nervous system. We have focused our studies on the adhesion molecule-like gp150 protein, which binds directly to and is an in vitro substrate for the RPTP DPTP10D. Here we show that gp150 and DPTP10D form stable complexes in Drosophila Schneider 2 (S2) cells and in wild-type larval tissue. We also demonstrate that the DPTP10D cytoplasmic domain is sufficient to confer binding to gp150. gp150 has a short cytoplasmic domain containing four tyrosines, all found within sequences similar to immunoreceptor family tyrosine-based activation motifs (ITAMs). We demonstrate that gp150 is tyrosine phosphorylated in wild-type larvae. In S2 cells, gp150 becomes tyrosine phosphorylated following incubation with PTP inhibitors or upon coexpression of the Dsrc tyrosine kinase. Phosphorylated Dsrc and an unknown 40-kDa phosphoprotein form stable complexes with gp150, thereby implicating them in a putative gp150 signaling pathway. When coexpressed with gp150, either full-length DPTP10D or its cytoplasmic domain mediates gp150 dephosphorylation whereas a catalytically inactive DPTP10D cytoplasmic domain does not. The neural RPTP DPTP99A can also induce gp150 dephosphorylation but does not coimmunoprecipitate with gp150. Taken together, the results suggest that gp150 transduces signals via phosphorylation of its ITAM-like elements. Phosphotyrosines on gp150 might function as binding sites for downstream signaling molecules, thereby initiating a signaling cascade that could be modulated in vivo by RPTPs such as DPTP10D.

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.

Design and Biological Evaluation of Novel Imidazolyl Flavonoids as Potent and Selective Protein Tyrosine Phosphatase Inhibitors

2020 ◽  
Vol 16 (4) ◽  
pp. 563-574 ◽  
Author(s):  
Rong Y. Han ◽  
Yu Ge ◽  
Ling Zhang ◽  
Qing M. Wang
Keyword(s):  
Protein Tyrosine Phosphatase ◽  
Tyrosine Phosphatase ◽  
Protein Tyrosine Phosphatases ◽  
Structural Features ◽  
Biological Evaluation ◽  
Cell Protein ◽  
Phosphatase Inhibitors ◽  
Protein Tyrosine ◽  
Therapeutic Development ◽  
Chemical Studies

Background: Protein tyrosine phosphatases 1B are considered to be a desirable validated target for therapeutic development of type II diabetes and obesity. Methods: A new series of imidazolyl flavonoids as potential protein tyrosine phosphatase inhibitors were synthesized and evaluated. Results: Bioactive results indicated that some synthesized compounds exhibited potent protein phosphatase 1B (PTP1B) inhibitory activities at the micromolar range. Especially, compound 8b showed the best inhibitory activity (IC50=1.0 µM) with 15-fold selectivity for PTP1B over the closely related T-cell protein tyrosine phosphatase (TCPTP). Cell viability assays indicated that 8b is cell permeable with lower cytotoxicity. Molecular modeling and dynamics studies revealed the reason for selectivity of PTP1B over TCPTP. Quantum chemical studies were carried out on these compounds to understand the structural features essential for activity. Conclusion: Compound 8b should be a potential selective PTP1B inhibitor.

scholarly journals Coordinated Regulation of Insulin Signaling by the Protein Tyrosine Phosphatases PTP1B and TCPTP

2005 ◽  
Vol 25 (2) ◽  
pp. 819-829 ◽  
Author(s):  
Sandra Galic ◽  
Christine Hauser ◽  
Barbara B. Kahn ◽  
Fawaz G. Haj ◽  
Benjamin G. Neel ◽  
...  
Keyword(s):  
Insulin Signaling ◽  
Tyrosine Phosphatase ◽  
Protein Tyrosine Phosphatases ◽  
Negative Regulator ◽  
Mitogen Activated Protein Kinase ◽  
Protein Tyrosine ◽  
Akt Activation ◽  
Protein Levels ◽  
Mitogen Activated Protein

ABSTRACT The protein tyrosine phosphatase PTP1B is a negative regulator of insulin signaling and a therapeutic target for type 2 diabetes. Our previous studies have shown that the closely related tyrosine phosphatase TCPTP might also contribute to the regulation of insulin receptor (IR) signaling in vivo (S. Galic, M. Klingler-Hoffmann, M. T. Fodero-Tavoletti, M. A. Puryer, T. C. Meng, N. K. Tonks, and T. Tiganis, Mol. Cell. Biol. 23:2096-2108, 2003). Here we show that PTP1B and TCPTP function in a coordinated and temporally distinct manner to achieve an overall regulation of IR phosphorylation and signaling. Whereas insulin-induced phosphatidylinositol 3-kinase/Akt signaling was prolonged in both TCPTP−/− and PTP1B−/− immortalized mouse embryo fibroblasts (MEFs), mitogen-activated protein kinase ERK1/2 signaling was elevated only in PTP1B-null MEFs. By using phosphorylation-specific antibodies, we demonstrate that both IR β-subunit Y1162/Y1163 and Y972 phosphorylation are elevated in PTP1B−/− MEFs, whereas Y972 phosphorylation was elevated and Y1162/Y1163 phosphorylation was sustained in TCPTP−/− MEFs, indicating that PTP1B and TCPTP differentially contribute to the regulation of IR phosphorylation and signaling. Consistent with this, suppression of TCPTP protein levels by RNA interference in PTP1B−/− MEFs resulted in no change in ERK1/2 signaling but caused prolonged Akt activation and Y1162/Y1163 phosphorylation. These results demonstrate that PTP1B and TCPTP are not redundant in insulin signaling and that they act to control both common as well as distinct insulin signaling pathways in the same cell.

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.

Protein-tyrosine phosphatase activity of CD45 is activated by sequential phosphorylation by two kinases

1994 ◽  
Vol 14 (8) ◽  
pp. 5523-5532
Author(s):  
D R Stover ◽  
K A Walsh
Keyword(s):  
T Cell Activation ◽  
Protein Tyrosine Phosphatase ◽  
Time Course ◽  
Cell Activation ◽  
Regulatory Mechanism ◽  
Transmembrane Protein ◽  
Tyrosine Phosphatase ◽  
Protein Tyrosine

We describe a potential regulatory mechanism for the transmembrane protein-tyrosine phosphatase CD45. Phosphorylation on both tyrosine and serine residues in vitro results in an activation of CD45 specifically toward one artificial substrate but not another. The activation of these kinases appears to be order dependent, as it is enhanced when phosphorylation of tyrosine precedes that of serine but phosphorylation in the reverse order yields no activation. Any of four protein-tyrosine kinases tested, in combination with the protein-serine/threonine kinase, casein kinase II, was capable of mediating this activation in vitro. The time course of phosphorylation of CD45 in response to T-cell activation is consistent with the possibility that this regulatory mechanism is utilized in vivo.

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