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  1. Article ; Online: A cell-based bioluminescence assay reveals dose-dependent and contextual repression of AP-1-driven gene expression by BACH2.

    Vardaka, Panagiota / Lozano, Teresa / Bot, Christopher / Ellery, Jonathan / Whiteside, Sarah K / Imianowski, Charlotte J / Farrow, Stuart / Walker, Simon / Okkenhaug, Hanneke / Yang, Jie / Okkenhaug, Klaus / Kuo, Paula / Roychoudhuri, Rahul

    Scientific reports

    2020  Volume 10, Issue 1, Page(s) 18902

    Abstract: Whereas effector ... ...

    Abstract Whereas effector CD4
    MeSH term(s) Acrylamides/pharmacology ; Animals ; Basic-Leucine Zipper Transcription Factors/genetics ; Cell Differentiation ; Dose-Response Relationship, Drug ; Gene Expression Regulation/drug effects ; Humans ; Jurkat Cells ; Luciferases/genetics ; Luciferases/metabolism ; Luminescent Measurements/methods ; Mice ; Phenylenediamines/pharmacology ; Tetracycline/pharmacology ; Tetradecanoylphorbol Acetate/analogs & derivatives ; Tetradecanoylphorbol Acetate/pharmacology ; Transcription Factor AP-1/genetics
    Chemical Substances Acrylamides ; BACH2 protein, human ; Basic-Leucine Zipper Transcription Factors ; Phenylenediamines ; RGFP966 ; Transcription Factor AP-1 ; phorbolol myristate acetate (56937-68-9) ; Luciferases (EC 1.13.12.-) ; Tetracycline (F8VB5M810T) ; Tetradecanoylphorbol Acetate (NI40JAQ945)
    Language English
    Publishing date 2020-11-03
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2615211-3
    ISSN 2045-2322 ; 2045-2322
    ISSN (online) 2045-2322
    ISSN 2045-2322
    DOI 10.1038/s41598-020-75732-z
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article: Possible mechanism for the alpha subunit of the interleukin-2 receptor (CD25) to influence interleukin-2 receptor signal transduction.

    Ellery, Jonathan M / Nicholls, Peter J

    Immunology and cell biology

    2002  Volume 80, Issue 4, Page(s) 351–357

    Abstract: The receptors for interleukin 2 (IL-2) and interleukin 15 (IL-15) in T cells share the IL-2R beta subunit (CD122) and gamma(C) subunit but have private alpha subunits. Despite utilizing the same receptor chains known to be necessary and sufficient to ... ...

    Abstract The receptors for interleukin 2 (IL-2) and interleukin 15 (IL-15) in T cells share the IL-2R beta subunit (CD122) and gamma(C) subunit but have private alpha subunits. Despite utilizing the same receptor chains known to be necessary and sufficient to transduce IL-2 signals the two cytokines manifest different cellular effects. It is commonly held that the alpha subunit of the IL-2R (CD25) is involved solely in the generation of a high affinity receptor complex. This is questioned by the development of autoimmune diseases in instances where the expression of CD25 is absent. The timely expression of CD25 in the thymus has been linked with clonal deletion. Evidence from peripheral T cells indicates that survival signals arising from the intermediate affinity IL-2R (lacking CD25) do not require the activation of Janus kinase 3 (Jak3) but do require the presence of the membrane proximal region of the gamma(C) chain. This particular signalling pathway is not observed in the high affinity receptor complex where Jak3 is activated. Recent data point to CD25 having a surface distribution consistent with it being localized within membrane microdomains. Here we suggest that in the absence of CD25 expression, IL-2R activation occurs within the soluble membrane fraction. This membrane environment and the absence of CD25 promotes Jak3 independent signal transduction and induction of antiapoptotic mechanisms. T cell antigen receptor (TCR) signalling leads to the induction of CD25 expression, which localizes to membrane microdomains. There is a dynamic pre-association of CD25 and CD122 leading to the loose association of the heterodimer with membrane microdomains. High affinity IL-2R signalling in the context of CD25 and the microdomain environment is characterized by Jak3 activation. The relative levels of high to intermediate affinity receptor signalling determines whether a cell proliferates or undergoes activation induced cell death dependent upon cell status.
    MeSH term(s) Animals ; Cell Membrane/chemistry ; Interleukin-15/physiology ; Interleukin-2/physiology ; Janus Kinase 3 ; Mice ; Models, Immunological ; Protein Subunits ; Protein-Tyrosine Kinases/physiology ; Receptors, Antigen, T-Cell/immunology ; Receptors, Interleukin-2/analysis ; Receptors, Interleukin-2/chemistry ; Receptors, Interleukin-2/metabolism ; Signal Transduction ; Thymus Gland/growth & development ; Thymus Gland/immunology
    Chemical Substances Interleukin-15 ; Interleukin-2 ; Protein Subunits ; Receptors, Antigen, T-Cell ; Receptors, Interleukin-2 ; Protein-Tyrosine Kinases (EC 2.7.10.1) ; Jak3 protein, mouse (EC 2.7.10.2) ; Janus Kinase 3 (EC 2.7.10.2)
    Language English
    Publishing date 2002-08
    Publishing country United States
    Document type Journal Article
    ZDB-ID 284057-1
    ISSN 1440-1711 ; 0818-9641
    ISSN (online) 1440-1711
    ISSN 0818-9641
    DOI 10.1046/j.1440-1711.2002.01097.x
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Identification of compounds acting as negative allosteric modulators of the LPA

    Ellery, Jonathan / Dickson, Louise / Cheung, Toni / Ciuclan, Loredana / Bunyard, Peter / Mack, Stephen / Buffham, William J / Farnaby, William / Mitchell, Philip / Brown, Daniel / Isaacs, Richard / Barnes, Matt

    European journal of pharmacology

    2018  Volume 833, Page(s) 8–15

    Abstract: The Lysophosphatidic Acid 1 Receptor ( ... ...

    Abstract The Lysophosphatidic Acid 1 Receptor (LPA
    MeSH term(s) Allosteric Regulation ; Animals ; Benzamides/chemistry ; Benzamides/pharmacology ; Benzoates/chemistry ; Benzoates/pharmacology ; Calcium/metabolism ; Cell Line, Tumor ; Cyclic AMP/metabolism ; Cyclopropanes/chemistry ; Cyclopropanes/pharmacology ; Indenes/chemistry ; Indenes/pharmacology ; Oxazoles/chemistry ; Oxazoles/pharmacology ; Rats ; Receptors, Lysophosphatidic Acid/antagonists & inhibitors ; Receptors, Lysophosphatidic Acid/metabolism
    Chemical Substances BMS-986202 ; Benzamides ; Benzoates ; Cyclopropanes ; Indenes ; Oxazoles ; Receptors, Lysophosphatidic Acid ; SAR-100842 ; TAK-615 ; Cyclic AMP (E0399OZS9N) ; Calcium (SY7Q814VUP)
    Language English
    Publishing date 2018-05-26
    Publishing country Netherlands
    Document type Journal Article
    ZDB-ID 80121-5
    ISSN 1879-0712 ; 0014-2999
    ISSN (online) 1879-0712
    ISSN 0014-2999
    DOI 10.1016/j.ejphar.2018.05.040
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article: Alternate signalling pathways from the interleukin-2 receptor.

    Ellery, Jonathan M / Nicholls, Peter J

    Cytokine & growth factor reviews

    2001  Volume 13, Issue 1, Page(s) 27–40

    Abstract: Interleukin-2 (IL-2) plays a major role in the proliferation of cell populations during an immune reaction. The beta(c) and gamma(c) subunits of the IL-2 receptor (IL-2R) are sufficient and necessary for signal transduction. Despite lacking known ... ...

    Abstract Interleukin-2 (IL-2) plays a major role in the proliferation of cell populations during an immune reaction. The beta(c) and gamma(c) subunits of the IL-2 receptor (IL-2R) are sufficient and necessary for signal transduction. Despite lacking known catalytic domains, receptor engagement leads to the activation of a diverse array protein tyrosine kinases (PTKs). In resting or anergised T cells, Jak3 is not activated. Signals arising from the PROX domain of the gamma(c) subunit activate p56(lck) (lck) leading to the induction of anti-apoptotic mechanisms. When Jak3 is activated, in primed T cells, other PTKs predominantly mediate the induction of anti-apoptotic mechanisms and drive cellular proliferation. This review intends to suggest a role for these differences within the context of the immune system.
    MeSH term(s) Animals ; Cell Division ; Dimerization ; Humans ; Interleukin-2/metabolism ; Janus Kinase 3 ; Mitogen-Activated Protein Kinase 1/metabolism ; Mitogen-Activated Protein Kinase 3 ; Mitogen-Activated Protein Kinases/metabolism ; Models, Biological ; Phosphatidylinositol 3-Kinases/metabolism ; Protein-Tyrosine Kinases/metabolism ; Receptors, Antigen, T-Cell/metabolism ; Receptors, Interleukin-2/metabolism ; Signal Transduction ; Transcription, Genetic
    Chemical Substances Interleukin-2 ; Receptors, Antigen, T-Cell ; Receptors, Interleukin-2 ; Phosphatidylinositol 3-Kinases (EC 2.7.1.-) ; Protein-Tyrosine Kinases (EC 2.7.10.1) ; JAK3 protein, human (EC 2.7.10.2) ; Janus Kinase 3 (EC 2.7.10.2) ; Mitogen-Activated Protein Kinase 1 (EC 2.7.11.24) ; Mitogen-Activated Protein Kinase 3 (EC 2.7.11.24) ; Mitogen-Activated Protein Kinases (EC 2.7.11.24)
    Language English
    Publishing date 2001-12-10
    Publishing country England
    Document type Journal Article ; Review
    ZDB-ID 1330534-7
    ISSN 1359-6101
    ISSN 1359-6101
    DOI 10.1016/s1359-6101(01)00023-5
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    Zs.A 2653: Show issues Location:
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  5. Article ; Online: Assessment of the Target Engagement and D-Serine Biomarker Profiles of the D-Amino Acid Oxidase Inhibitors Sodium Benzoate and PGM030756.

    Howley, Eimear / Bestwick, Michael / Fradley, Rosa / Harrison, Helen / Leveridge, Mathew / Okada, Kengo / Fieldhouse, Charlotte / Farnaby, Will / Canning, Hannah / Sykes, Andy P / Merchant, Kevin / Hazel, Katherine / Kerr, Catrina / Kinsella, Natasha / Walsh, Louise / Livermore, David G / Hoffman, Isaac / Ellery, Jonathan / Mitchell, Phillip /
    Patel, Toshal / Carlton, Mark / Barnes, Matt / Miller, David J

    Neurochemical research

    2017  Volume 42, Issue 11, Page(s) 3279–3288

    Abstract: Irregular N-methyl-D-aspartate receptor (NMDAR) function is one of the main hypotheses employed to facilitate understanding of the underlying disease state of schizophrenia. Although direct agonism of the NMDAR has not yielded promising therapeutics, ... ...

    Abstract Irregular N-methyl-D-aspartate receptor (NMDAR) function is one of the main hypotheses employed to facilitate understanding of the underlying disease state of schizophrenia. Although direct agonism of the NMDAR has not yielded promising therapeutics, advances have been made by modulating the NMDAR co-agonist site which is activated by glycine and D-serine. One approach to activate the co-agonist site is to increase synaptic D-serine levels through inhibition of D-amino acid oxidase (DAO), the major catabolic clearance pathway for this and other D-amino acids. A number of DAO inhibitors have been developed but most have not entered clinical trials. One exception to this is sodium benzoate which has demonstrated efficacy in small trials of schizophrenia and Alzheimer's disease. Herein we provide data on the effect of sodium benzoate and an optimised Takeda compound, PGM030756 on ex vivo DAO enzyme occupancy and cerebellar D-serine levels in mice. Both compounds achieve high levels of enzyme occupancy; although lower doses of PGM030756 (1, 3 and 10 mg/kg) were required to achieve this compared to sodium benzoate (300, 1000 mg/kg). Cerebellar D-serine levels were increased by both agents with a delay of approximately 6 h after dosing before the peak effect was achieved. Our data and methods may be useful in understanding the effects of sodium benzoate that have been seen in clinical trials of schizophrenia and Alzheimer's disease and to support the potential clinical assessment of other DAO inhibitors, such as PGM030756, which demonstrate good enzyme occupancy and D-serine increases following administration of low oral doses.
    MeSH term(s) Administration, Oral ; Animals ; Biomarkers/metabolism ; Cerebellum/metabolism ; Chlorobenzenes/administration & dosage ; Chlorobenzenes/chemistry ; Chlorobenzenes/pharmacology ; Crystallography, X-Ray ; D-Amino-Acid Oxidase/antagonists & inhibitors ; D-Amino-Acid Oxidase/metabolism ; Enzyme Inhibitors/administration & dosage ; Enzyme Inhibitors/chemistry ; Enzyme Inhibitors/pharmacology ; Humans ; Male ; Mice ; Mice, Inbred C57BL ; Pyridazines/administration & dosage ; Pyridazines/chemistry ; Pyridazines/pharmacology ; Serine/metabolism ; Sodium Benzoate/administration & dosage ; Sodium Benzoate/chemistry ; Sodium Benzoate/pharmacology
    Chemical Substances 6-((4-chlorophenyl)methyl)-4-hydroxy-2,3-dihydropyridazin-3-one ; Biomarkers ; Chlorobenzenes ; Enzyme Inhibitors ; Pyridazines ; Serine (452VLY9402) ; DAO protein, human (EC 1.4.3.-) ; D-Amino-Acid Oxidase (EC 1.4.3.3) ; Sodium Benzoate (OJ245FE5EU)
    Language English
    Publishing date 2017-11
    Publishing country United States
    Document type Journal Article
    ZDB-ID 199335-5
    ISSN 1573-6903 ; 0364-3190
    ISSN (online) 1573-6903
    ISSN 0364-3190
    DOI 10.1007/s11064-017-2367-9
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article ; Online: A fragment-based approach to identifying S-adenosyl-l-methionine -competitive inhibitors of catechol O-methyl transferase (COMT).

    Lanier, Marion / Ambrus, Geza / Cole, Derek C / Davenport, Richard / Ellery, Jonathan / Fosbeary, Richard / Jennings, Andy J / Kadotani, Akito / Kamada, Yusuke / Kamran, Ruhi / Matsumoto, Shin-Ichi / Mizukami, Atsushi / Okubo, Shoichi / Okada, Kengo / Saikatendu, Kumar / Walsh, Louise / Wu, Haihong / Hixon, Mark S

    Journal of medicinal chemistry

    2014  Volume 57, Issue 12, Page(s) 5459–5463

    Abstract: Catechol O-methyl transferase belongs to the diverse family of S-adenosyl-l-methionine transferases. It is a target involved in the treatment of Parkinson's disease. Here we present a fragment-based screening approach to discover noncatechol derived COMT ...

    Abstract Catechol O-methyl transferase belongs to the diverse family of S-adenosyl-l-methionine transferases. It is a target involved in the treatment of Parkinson's disease. Here we present a fragment-based screening approach to discover noncatechol derived COMT inhibitors which bind at the SAM binding pocket. We describe the identification and characterization of a series of highly ligand efficient SAM competitive bisaryl fragments (LE = 0.33-0.58). We also present the first SAM-competitive small-molecule COMT co-complex crystal structure.
    MeSH term(s) Animals ; Binding Sites ; Catechol O-Methyltransferase/chemistry ; Catechol O-Methyltransferase Inhibitors ; Humans ; Kinetics ; Mice ; Models, Molecular ; Protein Conformation ; Pyrazoles/chemistry ; Rats ; S-Adenosylmethionine/chemistry ; S-Adenosylmethionine/metabolism ; Structure-Activity Relationship ; Thiazoles/chemistry ; Triazoles/chemistry
    Chemical Substances Catechol O-Methyltransferase Inhibitors ; Pyrazoles ; Thiazoles ; Triazoles ; S-Adenosylmethionine (7LP2MPO46S) ; Catechol O-Methyltransferase (EC 2.1.1.6)
    Language English
    Publishing date 2014-06-26
    Publishing country United States
    Document type Journal Article
    ZDB-ID 218133-2
    ISSN 1520-4804 ; 0022-2623
    ISSN (online) 1520-4804
    ISSN 0022-2623
    DOI 10.1021/jm500475k
    Database MEDical Literature Analysis and Retrieval System OnLINE

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