Kinetics, substrate specificity, and stereospecificity of two new protein tyrosine phosphatase-like inositol polyphosphatases from Selenomonas lacticifex

2008 ◽  
Vol 86 (4) ◽  
pp. 322-330 ◽  
Author(s):  
Aaron A. Puhl ◽  
Ralf Greiner ◽  
L. Brent Selinger
Keyword(s):  
Protein Tyrosine Phosphatase ◽  
High Performance ◽  
Tyrosine Phosphatase ◽  
Inositol Polyphosphates ◽  
Protein Tyrosine ◽  
Ion Pair Chromatography ◽  
Inositol Tetrakisphosphate ◽  
Strict Specificity ◽  
New Protein

Inositol polyphosphatases (IPPases) play an important role in the metabolism of inositol polyphosphates, a class of molecules involved in signal transduction. Here we characterize 2 new protein tyrosine phosphatase-like IPPases (PhyAsl and PhyBsl) cloned from Selenomonas lacticifex that can hydrolyze myo-inositol hexakisphosphate (InsP6) in vitro. To determine their preferred substrates and stereospecificity of InsP6 dephosphorylation, a combination of kinetic and high-performance ion pair chromatography studies were conducted. Despite only 33% amino acid sequence identity between them, both enzymes display strict specificity for IPP substrates and cleave InsP6 primarily at the d-3-phosphate position (>90%). Furthermore, both enzymes predominantly degrade InsP6 to Ins(2)P via identical and very specific routes of dephosphorylation (3,4,5,6,1). Despite these similarities, PhylAsl is shown to have a slight kinetic preference for the major inositol pentakisphosphate intermediate in its InsP6 hydrolysis pathway, whereas PhyBsl displays a unique and substantial preference for an inositol tetrakisphosphate intermediate.

Analysis of in vitro interactions of protein tyrosine phosphatase 1B with insulin receptors

2001 ◽  
Vol 173 (1-2) ◽  
pp. 109-120 ◽  
Author(s):  
Xin-Yuan Wang ◽  
Katrin Bergdahl ◽  
Anna Heijbel ◽  
Charlotta Liljebris ◽  
John E. Bleasdale
Keyword(s):  
Protein Tyrosine Phosphatase ◽  
Tyrosine Phosphatase ◽  
Insulin Receptors ◽  
Protein Tyrosine Phosphatase 1B ◽  
Protein Tyrosine ◽  
In Vitro Interactions

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.

scholarly journals Six New 3,5-Dimethylcoumarins from Chelonopsis praecox, Chelonopsis odontochila and Chelonopsis pseudobracteata

2021 ◽  
Author(s):  
Chang-An Geng ◽  
Zhen-Tao Deng ◽  
Qian Huang ◽  
Chun-Lei Xiang ◽  
Ji-Jun Chen
Keyword(s):  
Protein Tyrosine Phosphatase ◽  
Tyrosine Phosphatase ◽  
2D Nmr ◽  
Cell Protein ◽  
Protein Tyrosine Phosphatase 1B ◽  
Protein Tyrosine ◽  
Aerial Parts ◽  
Spectroscopic Analyses ◽  
New Compounds

AbstractTen 3,5-dimethylcoumarins (1–6 and 8‒11) involving six new ones (1–6), together with a known 3-methylcoumarin (7), were isolated from the aerial parts of three Chelonopsis plants, C. praecox, C. odontochila, and C. pseudobracteata. The structures of the new compounds were determined by extensive HRESIMS, 1D and 2D NMR spectroscopic analyses. According to the substitution at C-5, these coumarins were classified into 5-methyl, 5-hydroxymethyl, 5-formyl, and 5-nor types. All the isolates were assayed for their inhibition on α-glucosidase, protein tyrosine phosphatase 1B, and T-cell protein tyrosine phosphatase in vitro. Graphic Abstract

scholarly journals Simulasi Docking Senyawa Aglikon Kurkuligosida A dan Turunannya pada Protein Tyrosine Phosphatase 1B (PTP1B)

2019 ◽  
Vol 16 (2) ◽  
pp. 216
Author(s):  
Nursamsiar Nursamsiar ◽  
Akbar Awaluddin ◽  
Megawati Megawati ◽  
Yulita M. Soko ◽  
Muhammad Aswad
Keyword(s):  
Protein Tyrosine Phosphatase ◽  
Tyrosine Phosphatase ◽  
Protein Tyrosine Phosphatase 1B ◽  
Protein Tyrosine ◽  
Autodock 4.2 ◽  
Diabetes Melitus

Senyawa aglikon kurkuligosida A memiliki struktur yang mirip dengan senyawa licoagrochalcone yang terbukti memiliki aktivitas penghambatan yang kuat secara in vitro pada Protein Tyrosine Phosphatase 1B (PTP1B), yang dianggap sebagai target terapeutik untuk pengobatan diabetes melitus tipe 2. Penelitian ini bertujuan untuk mengetahui interaksi antara senyawa aglikon kurkuligosida A dan turunannya dengan PTP1B menggunakan metode simulasi docking. Simulasi docking dilakukan dengan menggunakan perangkat lunak AutoDock 4.2. Hasil docking menunjukan semua senyawa yang diuji dapat berinteraksi dengan sisi aktif PTP1B. Interaksi terbaik ditunjukkan oleh senyawa 31 (3,5-dihidroksibensil-3,5-dinitrobenzoate), senyawa 39 (3,5-dihidroksibensil-4-nitrobenzoate) dan senyawa 52 (4-hidroksibensil-4-nitro bensoat) dengan nilai energi bebas ikatan berturut-turut –9,40 kkal/mol ; –9,19 kkal/mol dan –9,03 kkal/mol. Ketiga senyawa tersebut memiliki interaksi dengan sisi aktif PTP1B dengan residu asam amino Ser216 dan Arg221. Semua senyawa turunan aglikon kurkuligosida A yang diuji juga memiliki pola pengikatan yang sama dengan ligan alami pada PTP1B.

In Vitro Enzymatic Assays of Protein Tyrosine Phosphatase 1B

2001 ◽  
Vol 13 (1) ◽  
Author(s):  
Thomas Lubben ◽  
Jill Clampit ◽  
Michael Stashko ◽  
James Trevillyan ◽  
Michael R. Jirousek
Keyword(s):  
Protein Tyrosine Phosphatase ◽  
Tyrosine Phosphatase ◽  
Protein Tyrosine Phosphatase 1B ◽  
Enzymatic Assays ◽  
Protein Tyrosine

Selective Inhibitors of the Protein Tyrosine Phosphatase SHP2 Block Cellular Motility and Growth of Cancer Cells in vitro and in vivo

ChemMedChem ◽  
2015 ◽  
Vol 10 (5) ◽  
pp. 815-826 ◽  
Author(s):  
Stefanie Grosskopf ◽  
Chris Eckert ◽  
Christoph Arkona ◽  
Silke Radetzki ◽  
Kerstin Böhm ◽  
...  
Keyword(s):  
Cancer Cells ◽  
Protein Tyrosine Phosphatase ◽  
Tyrosine Phosphatase ◽  
Cellular Motility ◽  
Selective Inhibitors ◽  
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.

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