The Catalytic Role of Aspartic Acid-92 in the Human Dual-Specific Protein-Tyrosine-Phosphatase Vaccinia H1-Related

Abstract We previously demonstrated that the gene encoding PTPROt, the truncated form of protein tyrosine phosphatase receptor type O expressed predominantly in hematopoietic cells, is a candidate tumor suppressor and is down-regulated in chronic lymphocytic leukemia (CLL). Here, we show that PTPROt expression is significantly reduced in CD19+ spleen B cells from Eμ-T cell leukemia 1 (TCL1) transgenic mice relative to the wild-type mice. Strikingly, as much as a 60% decrease in PTPROt expression occurs at 7 weeks independently of promoter methylation. To elucidate the potential mechanism for this early suppression of PTPROt in these mice, we explored the role of activating protein-1 (AP-1) in its expression. We first demonstrate that AP-1 activation by 12-O-tetradecanoylphorbol-13-acetate induces PTPROt expression with concurrent recruitment of c-fos and c-jun to its promoter. The PTPROt promoter is also responsive to over- and underexpression of AP-1, confirming the role of AP-1 in PTPROt expression. Next, we demonstrate that TCL1 can repress the PTPROt promoter by altering c-fos expression and c-jun activation state. Finally, using primary CLL cells we have shown an inverse relationship between TCL1 and PTPROt expression. These findings further substantiate the role of TCL1 in PTPROt suppression and its importance in the pathogenesis of CLL.

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The role of T‐cell protein tyrosine phosphatase in epithelial carcinogenesis

Molecular Carcinogenesis ◽

10.1002/mc.23078 ◽

2019 ◽

Vol 58 (9) ◽

pp. 1640-1647

Author(s):

Liza D. Morales ◽

Anna K. Archbold ◽

Serena Olivarez ◽

Thomas J. Slaga ◽

John DiGiovanni ◽

...

Keyword(s):

T Cell ◽

Protein Tyrosine Phosphatase ◽

Tyrosine Phosphatase ◽

Cell Protein ◽

Protein Tyrosine

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Increased Proteolytic Processing of Protein Tyrosine Phosphatase μ in Confluent Vascular Endothelial Cells: The Role of PC5, a Member of the Subtilisin Family†

Biochemistry ◽

10.1021/bi952552d ◽

1996 ◽

Vol 35 (12) ◽

pp. 3797-3802 ◽

Cited By ~ 45

Author(s):

Michel Campan ◽

Masao Yoshizumi ◽

Nabil G. Seidah ◽

Mu-En Lee ◽

Cesario Bianchi ◽

...

Keyword(s):

Endothelial Cells ◽

Protein Tyrosine Phosphatase ◽

Vascular Endothelial Cells ◽

Tyrosine Phosphatase ◽

Proteolytic Processing ◽

Vascular Endothelial ◽

Protein Tyrosine

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Setaria cervidual specific phosphatase: characterization and its effect on eosinophil degranulation

Parasitology ◽

10.1017/s0031182009006271 ◽

2009 ◽

Vol 136 (8) ◽

pp. 895-904 ◽

Cited By ~ 5

Author(s):

S. RATHAUR ◽

R. RAI ◽

E. SRIKANTH ◽

S. SRIVASTAVA

Keyword(s):

Protein Tyrosine Phosphatase ◽

Tyrosine Phosphatase ◽

Gel Filtration ◽

Specific Protein ◽

Enzyme Concentration ◽

Cross Reactivity ◽

Filarial Parasite ◽

Significant Activity ◽

Protein Tyrosine

SUMMARYSetaria cervi, a bovine filarial parasite contains significant acid phosphatase (AcP) activity in its various life stages. Two forms of AcP were separated from somatic extract of adult female parasite using cation exchange, gel filtration and concavalin affinity chromatography. One form having a molecular mass of 79 kDa was characterized as dual specific protein tyrosine phosphatase (ScDSP) based on substrate specificity and inhibition studies. With various substrates tested, it showed significant activity in the order of phospho-L-tyrosine>pNPP>ADP>phospho-L-serine. Inhibition by orthovanadate, fluoride, molybdate, and zinc ions further confirms protein tyrosine phosphatase nature of the enzyme. Km and Vmax determined with various substrates were found to be 16·66 mM, 25·0 μM/ml/min with pNPP; 20·0 mM, 40·0 μM/ml/min with phospho-L-tyrosine and 27·0 mM, 25·0 μM/ml/min with phospho-L-serine. KIwith pNPP and sodium orthovanadate (IC5033·0 μM) was calculated to be 50·0 mM. Inhibition with pHMB, silver nitrate, DEPC and EDAC suggested the presence of cysteine, histidine and carboxylate residues at its active site. Cross-reactivity withW. bancrofti-infected sera was demonstrated by Western blotting. ScDSP showed elevated levels of IgE in chronic filarial sera using ELISA. Underin vitroconditions, ScDSP resulted in increased effector function of human eosinophils when stimulated by IgG, which showed a further decrease with increasing enzyme concentration. Results presented here suggest thatS. cerviDSP should be further studied to determine its role in pathogenesis and the persistence of filarial parasite.

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The role of receptor protein tyrosine phosphatase α in neuronal differentiation of embryonic stem cells

Developmental Brain Research ◽

10.1016/0165-3806(95)00186-7 ◽

1996 ◽

Vol 91 (2) ◽

pp. 304-307 ◽

Cited By ~ 9

Author(s):

Wouter G. van Inzen ◽

Maikel P. Peppelenbosch ◽

Maria W.M. van den Brand ◽

Leon G.J. Tertoolen ◽

Siegfried de Laat

Keyword(s):

Stem Cells ◽

Embryonic Stem Cells ◽

Neuronal Differentiation ◽

Protein Tyrosine Phosphatase ◽

Tyrosine Phosphatase ◽

Embryonic Stem ◽

Receptor Protein ◽

Protein Tyrosine ◽

Receptor Protein Tyrosine Phosphatase

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Control of Dendritic Cell Migration, T Cell-Dependent Immunity, and Autoimmunity by Protein Tyrosine Phosphatase PTPN12 Expressed in Dendritic Cells

Molecular and Cellular Biology ◽

10.1128/mcb.01369-13 ◽

2013 ◽

Vol 34 (5) ◽

pp. 888-899 ◽

Cited By ~ 29

Author(s):

Inmoo Rhee ◽

Ming-Chao Zhong ◽

Boris Reizis ◽

Cheolho Cheong ◽

André Veillette

Keyword(s):

Dendritic Cells ◽

T Cell ◽

Protein Tyrosine Phosphatase ◽

Tyrosine Phosphatase ◽

Genetically Engineered ◽

Lymphoid Tissues ◽

Peripheral Tissues ◽

Protein Tyrosine

Dendritic cells (DCs) capture and process antigens in peripheral tissues, migrate to lymphoid tissues, and present the antigens to T cells. PTPN12, also known as PTP-PEST, is an intracellular protein tyrosine phosphatase (PTP) involved in cell-cell and cell-substratum interactions. Herein, we examined the role of PTPN12 in DCs, using a genetically engineered mouse lacking PTPN12 in DCs. Our data indicated that PTPN12 was not necessary for DC differentiation, DC maturation, or cytokine production in response to inflammatory stimuli. However, it was needed for full induction of T cell-dependent immune responsesin vivo. This function largely correlated with the need of PTPN12 for DC migration from peripheral sites to secondary lymphoid tissues. Loss of PTPN12 in DCs resulted in hyperphosphorylation of the protein tyrosine kinase Pyk2 and its substrate, the adaptor paxillin. Pharmacological inhibition of Pyk2 or downregulation of Pyk2 expression also compromised DC migration, suggesting that Pyk2 deregulation played a pivotal role in the migration defect caused by PTPN12 deficiency. Together, these findings identified PTPN12 as a key regulator in the ability of DCs to induce antigen-induced T cell responses. This is due primarily to the role of PTPN12 in DC migration from peripheral sites to secondary lymphoid organs through regulation of Pyk2.

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