{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T05:27:11Z","timestamp":1790832431040,"version":"4.1.0"},"reference-count":41,"publisher":"National Academy of Sciences","issue":"35","license":[{"start":{"date-parts":[[2020,8,17]],"date-time":"2020-08-17T00:00:00Z","timestamp":1597622400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000011","name":"Howard Hughes Medical Institute","doi-asserted-by":"publisher","award":["55007416"],"award-info":[{"award-number":["55007416"]}],"id":[{"id":"10.13039\/100000011","id-type":"DOI","asserted-by":"publisher"}]},{"name":"EU Horizon 2020 Research and Innovation Program","award":["739593"],"award-info":[{"award-number":["739593"]}]},{"DOI":"10.13039\/501100003825","name":"Magyar Tudom\u00e1nyos Akad\u00e9mia","doi-asserted-by":"publisher","award":["LP2017-14\/2017"],"award-info":[{"award-number":["LP2017-14\/2017"]}],"id":[{"id":"10.13039\/501100003825","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000897","name":"Cystic Fibrosis Foundation","doi-asserted-by":"publisher","award":["CSANAD19G0"],"award-info":[{"award-number":["CSANAD19G0"]}],"id":[{"id":"10.13039\/100000897","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100011019","name":"Nemzeti Kutat\u00e1si, Fejleszt\u00e9si \u00e9s Innov\u00e1ci\u00f3s Hivatal","doi-asserted-by":"crossref","award":["PD 131643"],"award-info":[{"award-number":["PD 131643"]}],"id":[{"id":"10.13039\/501100011019","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2020,9]]},"abstract":"<jats:title>Significance<\/jats:title>\n                  <jats:p>Ion channels are protein pores that pass ions across biological membranes. CFTR is an anion channel required for proper salt\u2013water transport across epithelia, including the lung and the gut. CFTR overactivation due to bacterial toxins causes severe diarrhea (e.g., in cholera), and impaired activation due to mutations underlies cystic fibrosis, a lethal disease. CFTR is activated by a kinase (PKA) which phosphorylates the channel. Here we show that CFTR activation is not caused by phosphorylation, as believed, but by simple PKA binding which promotes reversible release of CFTR\u2019s regulatory (R) domain from an inhibitory position. Subsequent R-domain phosphorylation renders activation irreversible. Reversible channel activation is likely mediated by several members of a large protein network that interacts with CFTR.<\/jats:p>","DOI":"10.1073\/pnas.2007910117","type":"journal-article","created":{"date-parts":[[2020,8,17]],"date-time":"2020-08-17T20:45:28Z","timestamp":1597697128000},"page":"21740-21746","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":43,"title":["Simple binding of protein kinase A prior to phosphorylation allows CFTR anion channels to be opened by nucleotides"],"prefix":"10.1073","volume":"117","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7536-3066","authenticated-orcid":false,"given":"Csaba","family":"Mih\u00e1lyi","sequence":"first","affiliation":[{"name":"Department of Medical Biochemistry, Semmelweis University, H-1094 Budapest, Hungary;"},{"name":"Magyar Tudom\u00e1nyos Akad\u00e9mia - Semmelweis Egyetem (MTA-SE) Ion Channel Research Group, Semmelweis University, H-1094 Budapest, Hungary;"},{"name":"Hungarian Center of Excellence for Molecular Medicine - Semmelweis Egyetem (HCEMM-SE) Molecular Channelopathies Research Group, Semmelweis University, H-1094 Budapest, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8251-5857","authenticated-orcid":false,"given":"Iordan","family":"Iordanov","sequence":"additional","affiliation":[{"name":"Department of Medical Biochemistry, Semmelweis University, H-1094 Budapest, Hungary;"},{"name":"Magyar Tudom\u00e1nyos Akad\u00e9mia - Semmelweis Egyetem (MTA-SE) Ion Channel Research Group, Semmelweis University, H-1094 Budapest, Hungary;"},{"name":"Hungarian Center of Excellence for Molecular Medicine - Semmelweis Egyetem (HCEMM-SE) Molecular Channelopathies Research Group, Semmelweis University, H-1094 Budapest, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Be\u00e1ta","family":"T\u00f6r\u00f6csik","sequence":"additional","affiliation":[{"name":"Department of Medical Biochemistry, Semmelweis University, H-1094 Budapest, Hungary;"},{"name":"Magyar Tudom\u00e1nyos Akad\u00e9mia - Semmelweis Egyetem (MTA-SE) Ion Channel Research Group, Semmelweis University, H-1094 Budapest, Hungary;"},{"name":"Hungarian Center of Excellence for Molecular Medicine - Semmelweis Egyetem (HCEMM-SE) Molecular Channelopathies Research Group, Semmelweis University, H-1094 Budapest, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6547-5889","authenticated-orcid":false,"given":"L\u00e1szl\u00f3","family":"Csan\u00e1dy","sequence":"additional","affiliation":[{"name":"Department of Medical Biochemistry, Semmelweis University, H-1094 Budapest, Hungary;"},{"name":"Magyar Tudom\u00e1nyos Akad\u00e9mia - Semmelweis Egyetem (MTA-SE) Ion Channel Research Group, Semmelweis University, H-1094 Budapest, Hungary;"},{"name":"Hungarian Center of Excellence for Molecular Medicine - Semmelweis Egyetem (HCEMM-SE) Molecular Channelopathies Research Group, Semmelweis University, H-1094 Budapest, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2020,8,17]]},"reference":[{"key":"e_1_3_4_1_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.2475911"},{"key":"e_1_3_4_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(92)90155-6"},{"key":"e_1_3_4_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/S2213-2600(16)00023-0"},{"key":"e_1_3_4_4_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.2000.278.2.C417"},{"key":"e_1_3_4_5_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.275.19.14360"},{"key":"e_1_3_4_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(91)90446-6"},{"key":"e_1_3_4_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(18)42339-3"},{"key":"e_1_3_4_8_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.270.5.2158"},{"key":"e_1_3_4_9_2","doi-asserted-by":"publisher","DOI":"10.1002\/pro.5560061117"},{"key":"e_1_3_4_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.coph.2003.06.012"},{"key":"e_1_3_4_11_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.100588797"},{"key":"e_1_3_4_12_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature03313"},{"key":"e_1_3_4_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2016.11.014"},{"key":"e_1_3_4_14_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2017.02.024"},{"key":"e_1_3_4_15_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2017.06.041"},{"key":"e_1_3_4_16_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1815287115"},{"key":"e_1_3_4_17_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1712985"},{"key":"e_1_3_4_18_2","doi-asserted-by":"publisher","DOI":"10.1085\/jgp.116.3.477"},{"key":"e_1_3_4_19_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-3495(94)80668-X"},{"key":"e_1_3_4_20_2","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2005.095083"},{"key":"e_1_3_4_21_2","doi-asserted-by":"publisher","DOI":"10.1085\/jgp.201210954"},{"key":"e_1_3_4_22_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M609221200"},{"key":"e_1_3_4_23_2","doi-asserted-by":"publisher","DOI":"10.1085\/jgp.201010399"},{"key":"e_1_3_4_24_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ab.2005.02.008"},{"key":"e_1_3_4_25_2","first-page":"L127","article-title":"CFTR activation: Additive effects of stimulatory and inhibitory phosphorylation sites in the R domain","volume":"273","author":"Wilkinson D. J.","year":"1997","unstructured":"D. J. Wilkinson ., CFTR activation: Additive effects of stimulatory and inhibitory phosphorylation sites in the R domain. Am. J. Physiol. 273, L127\u2013L133 (1997).","journal-title":"Am. J. Physiol."},{"key":"e_1_3_4_26_2","doi-asserted-by":"publisher","DOI":"10.1085\/jgp.200409076"},{"key":"e_1_3_4_27_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(18)82125-1"},{"key":"e_1_3_4_28_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(20)80723-6"},{"key":"e_1_3_4_29_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1469-7793.1998.365bq.x"},{"key":"e_1_3_4_30_2","doi-asserted-by":"publisher","DOI":"10.1021\/bi00413a032"},{"key":"e_1_3_4_31_2","doi-asserted-by":"publisher","DOI":"10.1021\/cr000230w"},{"key":"e_1_3_4_32_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbapap.2003.11.029"},{"key":"e_1_3_4_33_2","doi-asserted-by":"publisher","DOI":"10.1016\/B978-0-12-398312-1.00012-3"},{"key":"e_1_3_4_34_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(17)34272-2"},{"key":"e_1_3_4_35_2","doi-asserted-by":"publisher","DOI":"10.1006\/bbrc.1995.1029"},{"key":"e_1_3_4_36_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1613546114"},{"key":"e_1_3_4_37_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature15729"},{"key":"e_1_3_4_38_2","doi-asserted-by":"publisher","DOI":"10.1038\/ncb1115"},{"key":"e_1_3_4_39_2","doi-asserted-by":"publisher","DOI":"10.1085\/jgp.116.2.163"},{"key":"e_1_3_4_40_2","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-4419-1229-9_18"},{"key":"e_1_3_4_41_2","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.44556"}],"container-title":["Proceedings of the National Academy of Sciences"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/www.pnas.org\/syndication\/doi\/10.1073\/pnas.2007910117","content-type":"unspecified","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/pnas.org\/doi\/pdf\/10.1073\/pnas.2007910117","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,4,13]],"date-time":"2022-04-13T07:21:52Z","timestamp":1649834512000},"score":1,"resource":{"primary":{"URL":"https:\/\/pnas.org\/doi\/full\/10.1073\/pnas.2007910117"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,8,17]]},"references-count":41,"journal-issue":{"issue":"35","published-print":{"date-parts":[[2020,9]]}},"alternative-id":["10.1073\/pnas.2007910117"],"URL":"https:\/\/doi.org\/10.1073\/pnas.2007910117","relation":{},"ISSN":["0027-8424","1091-6490"],"issn-type":[{"value":"0027-8424","type":"print"},{"value":"1091-6490","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,8,17]]},"assertion":[{"value":"2020-08-17","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}