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U.S.A."],"published-print":{"date-parts":[[2015,5,12]]},"abstract":"<jats:title>Significance<\/jats:title>\n                  <jats:p>The skin and intestinal barrier are controlled by signaling scissors, termed ADAM17 (a disintegrin and metalloprotease 17), that reside in the membrane on the surface of cells. The main purpose of these signaling scissors is to liberate growth factors from their membrane anchor, allowing them to activate their receptors, including the epidermal growth factor receptor (EGFR). The ADAM17\/EGFR signaling axis is tightly regulated, yet little is known about the underlying mechanism. Here we use genetic, cell biological, and biochemical approaches to identify two membrane proteins termed iRhoms 1 and 2 (inactive Rhomboid-like proteins) as crucial upstream regulators of ADAM17-dependent EGFR signaling. This uncovers the iRhoms as attractive novel targets to treat ADAM17\/EGFR-dependent diseases such as cancer.<\/jats:p>","DOI":"10.1073\/pnas.1505649112","type":"journal-article","created":{"date-parts":[[2015,4,30]],"date-time":"2015-04-30T17:24:52Z","timestamp":1430414692000},"page":"6080-6085","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":148,"title":["iRhoms 1 and 2 are essential upstream regulators of ADAM17-dependent EGFR signaling"],"prefix":"10.1073","volume":"112","author":[{"given":"Xue","family":"Li","sequence":"first","affiliation":[{"name":"Arthritis and Tissue Degeneration Program and"},{"name":"Departments of bBiochemistry, Cell and Molecular Biology,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thorsten","family":"Maretzky","sequence":"additional","affiliation":[{"name":"Arthritis and Tissue Degeneration Program and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gisela","family":"Weskamp","sequence":"additional","affiliation":[{"name":"Arthritis and Tissue Degeneration Program and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S\u00e9bastien","family":"Monette","sequence":"additional","affiliation":[{"name":"Tri-Institutional Laboratory of Comparative Pathology, New York, NY 10021;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoping","family":"Qing","sequence":"additional","affiliation":[{"name":"Autoimmunity and Inflammation Program, Hospital for Special Surgery, New York, NY 10021;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Priya Darshinee A.","family":"Issuree","sequence":"additional","affiliation":[{"name":"Arthritis and Tissue Degeneration Program and"},{"name":"Immunology, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Howard C.","family":"Crawford","sequence":"additional","affiliation":[{"name":"Department of Cancer Biology, Mayo Clinic Cancer Center, Jacksonville, FL 32224;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David R.","family":"McIlwain","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Hepatology, and Infectious Diseases, Heinrich Heine University, D-40225 Dusseldorf, Germany;"},{"name":"Baxter Laboratory in Stem Cell Biology, Department of Microbiology and Immunology, Stanford University, Stanford, CA 94305; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tak W.","family":"Mak","sequence":"additional","affiliation":[{"name":"Campbell Family Institute for Breast Cancer Research, Princess Margaret Cancer Center, University Health Network, Toronto, ON, Canada M5G 2M9"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jane E.","family":"Salmon","sequence":"additional","affiliation":[{"name":"Autoimmunity and Inflammation Program, Hospital for Special Surgery, New York, NY 10021;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carl P.","family":"Blobel","sequence":"additional","affiliation":[{"name":"Arthritis and Tissue Degeneration Program and"},{"name":"Physiology, Biophysics and Systems Biology, Weill Cornell Graduate School of Medical Sciences, New York, NY 10021;"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2015,4,27]]},"reference":[{"key":"e_1_3_3_1_2","doi-asserted-by":"publisher","DOI":"10.1038\/385729a0"},{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1038\/385733a0"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.282.5392.1281"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.200307137"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M112050200"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1038\/376337a0"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.7618084"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.7618085"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1242\/dev.00664"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.00291-13"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.179.5.2686"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1093\/emboj\/cdg264"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1242\/dev.02030"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0537588100"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1100721"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrc1970"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.3005886"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1038\/jid.2014.164"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20112258"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20092366"},{"key":"e_1_3_3_21_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrm1548"},{"key":"e_1_3_3_22_2","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.069997"},{"key":"e_1_3_3_23_2","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms1232"},{"key":"e_1_3_3_24_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1214400"},{"key":"e_1_3_3_25_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1216815"},{"key":"e_1_3_3_26_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1214448"},{"key":"e_1_3_3_27_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1302553110"},{"key":"e_1_3_3_28_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2012-03-417949"},{"key":"e_1_3_3_29_2","first-page":"928","article-title":"iRHOM2 is a critical pathogenic mediator of inflammatory arthritis","volume":"123","author":"Issuree PD","year":"2013","unstructured":"PD Issuree, , iRHOM2 is a critical pathogenic mediator of inflammatory arthritis. 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