0000000000026108

AUTHOR

Jana V. Maier

showing 3 related works from this author

Aplidin® induces JNK-dependent apoptosis in human breast cancer cells via alteration of glutathione homeostasis, Rac1 GTPase activation, and MKP-1 ph…

2006

Aplidin® is an antitumor agent in phase II clinical trials that induces apoptosis through the sustained activation of Jun N-terminal kinase (JNK). We report that Aplidin® alters glutathione homeostasis increasing the ratio of oxidized to reduced forms (GSSG/GSH). Aplidin® generates reactive oxygen species and disrupts the mitochondrial membrane potential. Exogenous GSH inhibits these effects and also JNK activation and cell death. We found two mechanisms by which Aplidin® activates JNK: rapid activation of Rac1 small GTPase and downregulation of MKP-1 phosphatase. Rac1 activation was diminished by GSH and enhanced by L-buthionine (SR)-sulfoximine, which inhibits GSH synthesis. Downregulatio…

rac1 GTP-Binding ProteinProgrammed cell deathSmall interfering RNAGlutathione reductaseDown-RegulationAntineoplastic AgentsApoptosisBreast NeoplasmsCell Cycle ProteinsBiologyPeptides CyclicImmediate-Early ProteinsMembrane Potentialschemistry.chemical_compoundMiceDownregulation and upregulationDepsipeptidesProtein Phosphatase 1Phosphoprotein PhosphatasesAnimalsHomeostasisHumansMolecular Biologychemistry.chemical_classificationReactive oxygen speciesGlutathione PeroxidaseGlutathione DisulfideJNK Mitogen-Activated Protein KinasesProtein phosphatase 1Dual Specificity Phosphatase 1Cell BiologyGlutathioneCell biologyEnzyme ActivationOxidative StressGlutathione ReductasechemistryMitochondrial MembranesGlutathione disulfideCalciumProtein Tyrosine PhosphatasesReactive Oxygen SpeciesCopperHeLa CellsCell Death and Differentiation
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Dual specificity phosphatase 1 knockout mice show enhanced susceptibility to anaphylaxis but are sensitive to glucocorticoids.

2007

Dual specificity phosphatase DUSP1 (otherwise known as mitogen-activated phosphatase 1 or MKP-1) dephosphorylates MAPKs, particularly p38, and negatively regulates innate immunity. Recent studies have shown that the DUSP1 gene is transcriptionally up-regulated by glucocorticoids (GCs) and that the antiinflammatory action of GCs is impaired in DUSP1-/- mice. Here we show that GC-mediated dephosphorylation of ERK-1 and ERK-2 activated by IgE receptor cross-linking is unimpaired in bone marrow-derived mast cells (BMMCs) of DUSP1-/- mice. Dephosphorylation of phospho-p38 MAPK is impaired but only at early times of GC treatment. Proinflammatory cytokine and chemokine gene expression (CCL2, IL-6,…

medicine.medical_specialtyChemokinePhosphataseImmunoglobulin Ep38 Mitogen-Activated Protein KinasesProinflammatory cytokineDephosphorylationMiceEndocrinologyInternal medicineSepsisDual-specificity phosphatasemedicineAnimalsGenetic Predisposition to DiseaseMolecular BiologyAnaphylaxisGlucocorticoidsMice KnockoutMitogen-Activated Protein Kinase 1Mice Inbred C3HMitogen-Activated Protein Kinase 3biologyInterleukin-6Tumor Necrosis Factor-alphaDegranulationDual Specificity Phosphatase 1General MedicineMice Inbred C57BLEndocrinologyGene Expression RegulationMice Inbred DBAbiology.proteinCytokinesTumor necrosis factor alphaMolecular endocrinology (Baltimore, Md.)
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PEST-domain-enriched tyrosine phosphatase and glucocorticoids as regulators of anaphylaxis in mice

2011

To cite this article: Obiri DD, Flink N, Maier JV, Neeb A, Maddalo D, Thiele W, Menon A, Stassen M, Kulkarni RA, Garabedian MJ, Barrios AM, Cato ACB. PEST-domain-enriched tyrosine phosphatase and glucocorticoids as regulators of anaphylaxis in mice. Allergy 2012; 67: 175–182. Abstract Background:  PEST-domain-enriched tyrosine phosphatase (PEP) is a protein tyrosine phosphatase exclusively expressed in hematopoietic cells. It is a potent negative regulator of T-cell receptor signalling that acts on receptor-coupled protein tyrosine kinases. PEST-domain-enriched tyrosine phosphatase is also expressed in mast cell and is positively regulated by glucocorticoids, but its function is unknown. In…

medicine.medical_specialtyeducationImmunologyDegranulationProtein tyrosine phosphataseBiologyImmunoglobulin EMast cellPTPN22Endocrinologymedicine.anatomical_structureInternal medicinecardiovascular systemmedicinebiology.proteinImmunology and AllergyPhosphorylationSignal transductionGlucocorticoidcirculatory and respiratory physiologymedicine.drugAllergy
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