{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T02:15:50Z","timestamp":1791252950722,"version":"4.1.0"},"reference-count":58,"publisher":"National Academy of Sciences","issue":"9","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2006,2,28]]},"abstract":"<jats:p>\n                    Many bacterial toxins act on conserved components of essential host-signaling pathways. One consequence of this conservation is that genetic model organisms such as\n                    <jats:italic>Drosophila melanogaster<\/jats:italic>\n                    can be used for analyzing the mechanism of toxin action. In this study, we characterize the activities of two anthrax virulence factors, lethal factor (LF) and edema factor, in transgenic\n                    <jats:italic>Drosophila<\/jats:italic>\n                    . LF is a zinc metalloprotease that cleaves and inactivates most human mitogen-activated protein kinase (MAPK) kinases (MAPKKs). We found that LF similarly cleaves the\n                    <jats:italic>Drosophila<\/jats:italic>\n                    MAPK kinases Hemipterous (Hep) and Licorne\n                    <jats:italic>in vitro<\/jats:italic>\n                    . Consistent with these observations, expression of LF in\n                    <jats:italic>Drosophila<\/jats:italic>\n                    inhibited the Hep\/c-Jun N-terminal kinase pathway during embryonic dorsal closure and the related process of adult thoracic closure. Epistasis experiments confirmed that LF acts at the level of Hep. We also found that LF inhibits Ras\/MAPK signaling during wing development and that LF acts upstream of MAPK and downstream of Raf, consistent with LF acting at the level of Dsor. In addition, we found that edema factor, a potent adenylate cyclase, inhibits the\n                    <jats:italic>hh<\/jats:italic>\n                    pathway during wing development, consistent with the known role of cAMP-dependent PKA in suppressing the Hedgehog response. These results demonstrate that anthrax toxins function in\n                    <jats:italic>Drosophila<\/jats:italic>\n                    as they do in mammalian cells and open the way to using\n                    <jats:italic>Drosophila<\/jats:italic>\n                    as a multicellular host system for studying the\n                    <jats:italic>in vivo<\/jats:italic>\n                    function of diverse toxins and virulence factors.\n                  <\/jats:p>","DOI":"10.1073\/pnas.0510748103","type":"journal-article","created":{"date-parts":[[2006,2,2]],"date-time":"2006-02-02T20:48:38Z","timestamp":1138913318000},"page":"3244-3249","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":41,"title":["Anthrax lethal factor and edema factor act on conserved targets in\n                    <i>Drosophila<\/i>"],"prefix":"10.1073","volume":"103","author":[{"given":"Annabel","family":"Guichard","sequence":"first","affiliation":[{"name":"Section of Cell and Developmental Biology, University of California at San Diego, 9500 Gilman Drive, La Jolla, CA 92093-0349;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jin Mo","family":"Park","sequence":"additional","affiliation":[{"name":"Laboratory of Gene Regulation and Signal Transduction, Department of Pharmacology, School of Medicine, University of California at San Diego, La Jolla, CA 92093; and"},{"name":"Cutaneous Biology Research Center, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA 02129"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Beatriz","family":"Cruz-Moreno","sequence":"additional","affiliation":[{"name":"Section of Cell and Developmental Biology, University of California at San Diego, 9500 Gilman Drive, La Jolla, CA 92093-0349;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Karin","sequence":"additional","affiliation":[{"name":"Laboratory of Gene Regulation and Signal Transduction, Department of Pharmacology, School of Medicine, University of California at San Diego, La Jolla, CA 92093; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ethan","family":"Bier","sequence":"additional","affiliation":[{"name":"Section of Cell and Developmental Biology, University of California at San Diego, 9500 Gilman Drive, La Jolla, CA 92093-0349;"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2006,2,2]]},"reference":[{"key":"e_1_3_3_1_2","doi-asserted-by":"publisher","DOI":"10.1101\/gr.169101"},{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrg1503"},{"key":"e_1_3_3_3_2","first-page":"25","volume-title":"Molecular Basis of Inborn Errors of Development","author":"Bier E.","year":"2004","unstructured":"E. 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