{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,19]],"date-time":"2025-10-19T21:14:14Z","timestamp":1760908454419},"reference-count":21,"publisher":"Proceedings of the National Academy of Sciences","issue":"16","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2008,4,22]]},"abstract":"<jats:p>Janus kinases (JAKs) and signal transducers and activators of transcription (STATs) are essential for responses to interferons (IFNs), most cytokines, and some growth factors. JAK\/STAT signaling is not, however, sufficient for a full IFN-\u03b3 response. Here, a convenient, robust, and quantitative flow cytometry-based kinome-wide siRNA screen has identified nine additional kinases as required for the IFN-\u03b3 class II HLA response, seven for an antiviral response, and two for the cytopathic response to encephalomyocarditis virus (EMCV). As one example, inhibition of the IFN-\u03b3 response by siRNA to ataxia telangiectasia-mutated (ATM) differentially affects a spectrum of IFN-\u03b3-stimulated mRNAs, with inhibitions being seen as early as 1 h after IFN-\u03b3 stimulation. The implication of ATM, with its previously recognized function in chromatin decondensation, in the control of transcription early in the IFN-\u03b3 response highlights both a role for ATM in cytokine responses and a possible correlation with the chromatin decondensation recently observed in response to IFN-\u03b3 in mammalian cells. This work has, therefore, revealed the simplicity, power, and convenience of quantitative flow cytometry-based siRNA screens, a requirement for ATM and multiple additional kinases in the IFN-\u03b3 response and a possible requirement for two of these kinases in the cytopathic response to EMCV.<\/jats:p>","DOI":"10.1073\/pnas.0710814105","type":"journal-article","created":{"date-parts":[[2008,4,16]],"date-time":"2008-04-16T01:49:41Z","timestamp":1208310581000},"page":"6051-6056","update-policy":"http:\/\/dx.doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":13,"title":["Multiple kinases in the interferon-\u03b3 response"],"prefix":"10.1073","volume":"105","author":[{"given":"D.","family":"Watling","sequence":"first","affiliation":[{"name":"*Department of Oncology, Imperial College London, Hammersmith Hospital Campus, Du Cane Road, London W12 0NN, United Kingdom; and"},{"name":"Cancer Research UK, London Research Institute, Lincoln's Inn Fields Laboratories, 44 Lincoln's Inn Fields, London WC2A 3PX, United Kingdom"}]},{"given":"C. R.","family":"Carmo","sequence":"additional","affiliation":[{"name":"*Department of Oncology, Imperial College London, Hammersmith Hospital Campus, Du Cane Road, London W12 0NN, United Kingdom; and"}]},{"given":"I. M.","family":"Kerr","sequence":"additional","affiliation":[{"name":"Cancer Research UK, London Research Institute, Lincoln's Inn Fields Laboratories, 44 Lincoln's Inn Fields, London WC2A 3PX, United Kingdom"}]},{"given":"A. P.","family":"Costa-Pereira","sequence":"additional","affiliation":[{"name":"*Department of Oncology, Imperial College London, Hammersmith Hospital Campus, Du Cane Road, London W12 0NN, United Kingdom; and"},{"name":"Cancer Research UK, London Research Institute, Lincoln's Inn Fields Laboratories, 44 Lincoln's Inn Fields, London WC2A 3PX, United Kingdom"}]}],"member":"341","published-online":{"date-parts":[[2008,4,22]]},"reference":[{"key":"e_1_3_3_1_2","doi-asserted-by":"publisher","DOI":"10.1038\/nri1961"},{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1038\/ni1213"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1038\/icb.1997.50"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1471-4906(01)02118-4"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1002\/j.1460-2075.1996.tb00415.x"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.122236099"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M105070200"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.052159099"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1038\/366129a0"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1038\/366166a0"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M300003200"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.01728"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1091\/mbc.e05-09-0858"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.012328"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M308166200"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng1860"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1038\/ncb1446"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1093\/emboj\/20.10.2508"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.1002\/j.1460-2075.1993.tb06106.x"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.8397445"},{"key":"e_1_3_3_21_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.onc.1201319"}],"container-title":["Proceedings of the National Academy of Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pnas.org\/doi\/pdf\/10.1073\/pnas.0710814105","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,4,12]],"date-time":"2022-04-12T20:00:27Z","timestamp":1649793627000},"score":1,"resource":{"primary":{"URL":"https:\/\/pnas.org\/doi\/full\/10.1073\/pnas.0710814105"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2008,4,22]]},"references-count":21,"journal-issue":{"issue":"16","published-print":{"date-parts":[[2008,4,22]]}},"alternative-id":["10.1073\/pnas.0710814105"],"URL":"https:\/\/doi.org\/10.1073\/pnas.0710814105","relation":{},"ISSN":["0027-8424","1091-6490"],"issn-type":[{"value":"0027-8424","type":"print"},{"value":"1091-6490","type":"electronic"}],"subject":[],"published":{"date-parts":[[2008,4,22]]},"assertion":[{"value":"2007-11-15","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2008-04-22","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}