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{"target":"http://pubannotation.org/docs/sourcedb/PMC/sourceid/2674207","sourcedb":"PMC","sourceid":"2674207","source_url":"http://www.ncbi.nlm.nih.gov/pmc/2674207","text":"What Did the Researchers Do and Find?\nTranscription factors have to move into the nucleus of cells (so-called nuclear translocation) to control the expression of their target genes, so the researchers first asked whether fluticasone affects the cellular localization of GATA-3. Fluticasone treatment of activated T lymphocytes growing in dishes, they report, inhibited the nuclear translocation of GATA-3 and reduced Th2 cytokine expression. Other experiments showed that the inhibition of GATA-3 nuclear translocation was partly caused by competition between the glucocorticoid receptor bound to fluticasone and GATA-3 for binding to importin-α, a protein that is required for nuclear import. However, fluticasone also prevented the nuclear translocation of GATA-3 in a second way. Before GATA-3 can bind to importin-α, phosphate groups have to be added to specific sites in GATA-3. This “phosphorylation” requires an enzyme called p38 MAP kinase, and the researchers found that fluticasone treatment of activated T lymphocytes induced the expression of MAP kinase phophatase-1, a p38 MAP kinase inhibitor. Finally, when the researchers treated seven patients with mild asthma with inhaled fluticasone, they found that fluticasone also inhibited GATA-3 nuclear translocation in the lymphocytes circulating in the patients' blood.","divisions":[{"label":"Title","span":{"begin":0,"end":37}}],"tracks":[{"project":"sentences","denotations":[{"id":"T35","span":{"begin":0,"end":37},"obj":"Sentence"},{"id":"T36","span":{"begin":38,"end":277},"obj":"Sentence"},{"id":"T37","span":{"begin":278,"end":441},"obj":"Sentence"},{"id":"T38","span":{"begin":442,"end":693},"obj":"Sentence"},{"id":"T39","span":{"begin":694,"end":782},"obj":"Sentence"},{"id":"T40","span":{"begin":783,"end":883},"obj":"Sentence"},{"id":"T41","span":{"begin":884,"end":1107},"obj":"Sentence"},{"id":"T42","span":{"begin":1108,"end":1330},"obj":"Sentence"}],"namespaces":[{"prefix":"_base","uri":"http://pubannotation.org/ontology/tao.owl#"}],"attributes":[{"subj":"T35","pred":"source","obj":"sentences"},{"subj":"T36","pred":"source","obj":"sentences"},{"subj":"T37","pred":"source","obj":"sentences"},{"subj":"T38","pred":"source","obj":"sentences"},{"subj":"T39","pred":"source","obj":"sentences"},{"subj":"T40","pred":"source","obj":"sentences"},{"subj":"T41","pred":"source","obj":"sentences"},{"subj":"T42","pred":"source","obj":"sentences"}]}],"config":{"attribute types":[{"pred":"source","value type":"selection","values":[{"id":"sentences","color":"#cdec93","default":true}]}]}}