{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T12:57:04Z","timestamp":1791205024170,"version":"4.1.0"},"reference-count":42,"publisher":"American Society for Microbiology","issue":"3","license":[{"start":{"date-parts":[[2014,3,1]],"date-time":"2014-03-01T00:00:00Z","timestamp":1393632000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Infect Immun"],"published-print":{"date-parts":[[2014,3]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            <jats:named-content content-type=\"genus-species\">Francisella tularensis<\/jats:named-content>\n            , the causative agent of tularemia, modulates the host immune response to gain a survival advantage within the host. One mechanism of immune evasion is the ability of\n            <jats:named-content content-type=\"genus-species\">F. tularensis<\/jats:named-content>\n            to induce the synthesis of the small lipid mediator prostaglandin E2 (PGE\n            <jats:sub>2<\/jats:sub>\n            ), which alters the host T cell response making the host more susceptible to\n            <jats:named-content content-type=\"genus-species\">Francisella<\/jats:named-content>\n            growth. PGE\n            <jats:sub>2<\/jats:sub>\n            is synthesized by a tightly regulated biosynthetic pathway following stimulation. The synthesis of PGE\n            <jats:sub>2<\/jats:sub>\n            begins with the liberation of arachidonic acid (AA) from membrane phospholipids by cytosolic phospholipase A2 (cPLA\n            <jats:sub>2<\/jats:sub>\n            ). AA is subsequently converted to the unstable intermediate PGH\n            <jats:sub>2<\/jats:sub>\n            by cyclooxygenase-2 (COX-2), and PGH\n            <jats:sub>2<\/jats:sub>\n            undergoes an isomerization reaction to generate PGE\n            <jats:sub>2<\/jats:sub>\n            . Our objective was to identify\n            <jats:named-content content-type=\"genus-species\">F. tularensis<\/jats:named-content>\n            -activated host signaling pathways that regulate the activity of the enzymes in the PGE\n            <jats:sub>2<\/jats:sub>\n            -biosynthetic pathway. In this study, we show that cPLA\n            <jats:sub>2<\/jats:sub>\n            , p38 mitogen-activated protein kinase (MAPK), and Janus kinase 3 (JAK3) signaling are necessary for\n            <jats:named-content content-type=\"genus-species\">F. tularensis<\/jats:named-content>\n            -induced PGE\n            <jats:sub>2<\/jats:sub>\n            production. Inhibition of JAK3 activity reduced the phosphorylation of cPLA\n            <jats:sub>2<\/jats:sub>\n            and COX-2 protein levels. In addition, JAK3 regulates cPLA\n            <jats:sub>2<\/jats:sub>\n            phosphorylation independent of transcription. Moreover, p38 MAPK activity is required for\n            <jats:named-content content-type=\"genus-species\">F. tularensis<\/jats:named-content>\n            -induced COX-2 protein synthesis, but not for the phosphorylation of cPLA\n            <jats:sub>2<\/jats:sub>\n            . This research highlights a unique signaling axis in which JAK3 and p38 MAPK regulate the activity of multiple enzymes of the PGE\n            <jats:sub>2<\/jats:sub>\n            -biosynthetic pathway in macrophages infected with\n            <jats:named-content content-type=\"genus-species\">F. tularensis<\/jats:named-content>\n            .\n          <\/jats:p>","DOI":"10.1128\/iai.01461-13","type":"journal-article","created":{"date-parts":[[2013,12,17]],"date-time":"2013-12-17T03:16:28Z","timestamp":1387250188000},"page":"970-982","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":16,"title":["Janus Kinase 3 Activity Is Necessary for Phosphorylation of Cytosolic Phospholipase A2 and Prostaglandin E2 Synthesis by Macrophages Infected with Francisella tularensis Live Vaccine Strain"],"prefix":"10.1128","volume":"82","author":[{"given":"Ashley M.","family":"Brummett","sequence":"first","affiliation":[{"name":"Department of Microbiology and Immunology, Louisiana State University Health Sciences Center at Shreveport, Shreveport, Louisiana, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aaron R.","family":"Navratil","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Louisiana State University Health Sciences Center at Shreveport, Shreveport, Louisiana, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joshua D.","family":"Bryan","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Louisiana State University Health Sciences Center at Shreveport, Shreveport, Louisiana, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew D.","family":"Woolard","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Louisiana State University Health Sciences Center at Shreveport, Shreveport, Louisiana, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1001\/archinte.1961.03620050068007"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0882-4010(03)00046-9"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2958.1998.00926.x"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.00207-13"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1128\/MMBR.05027-11"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.3389\/fmicb.2013.00016"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.178.4.2065"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.iy.02.040184.002003"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M204810200"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.00844-09"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1128\/iai.64.8.3288-3293.1996"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.01412-07"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.plefa.2003.12.012"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0163-7827(03)00037-7"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(93)90666-E"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1042\/BST0360543"},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(20)80554-7"},{"key":"e_1_3_2_19_2","doi-asserted-by":"publisher","DOI":"10.1186\/1465-9921-9-16"},{"key":"e_1_3_2_20_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.micpath.2005.02.003"},{"key":"e_1_3_2_21_2","doi-asserted-by":"publisher","DOI":"10.1006\/bbrc.1999.1454"},{"key":"e_1_3_2_22_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1349-7006.2008.01053.x"},{"key":"e_1_3_2_23_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.176.8.5050"},{"key":"e_1_3_2_24_2","first-page":"1569","article-title":"Structure-based design of specific inhibitors of Janus kinase 3 as apoptosis-inducing antileukemic agents","volume":"5","author":"Sudbeck EA","year":"1999","unstructured":"SudbeckEALiuXPNarlaRKMahajanSGhoshSMaoCUckunFM. 1999. 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