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In this study, we demonstrate a novel system to directly select functional intrabodies from a library in the mammalian cytoplasm. In this system, a target homo\u2010oligomeric antigen is expressed together with a single\u2010chain Fv (scFv) library that is linked to the cytoplasmic domain of a receptor tyrosine kinase (RTK) in the cytoplasm of murine interleukin\u20103 (IL\u20103)\u2010dependent cells. As the tyrosine kinase is activated by dimerization, only scFv\u2010RTK clones that can bind to the target antigen would be oligomerized and transduce a growth signal under the IL\u20103\u2010deprived condition, which leads to selection of functional intrabodies. To demonstrate this system, we used rabies virus phosphoprotein (RV\u2010P) that forms dimers in the cytoplasm as a target antigen. As a result, functional intrabodies were selected using our system from a na\u00efve scFv library as well as from a pre\u2010selected anti\u2010RV\u2010P library generated by phage display. This system may be applied for screening intrabodies that can prevent progression of various severe diseases.<\/jats:p>","DOI":"10.1002\/biot.201500364","type":"journal-article","created":{"date-parts":[[2015,12,9]],"date-time":"2015-12-09T02:01:25Z","timestamp":1449626485000},"page":"565-573","source":"Crossref","is-referenced-by-count":8,"title":["Growth signalobody selects functional intrabodies in the mammalian cytoplasm"],"prefix":"10.1002","volume":"11","author":[{"given":"Songhee","family":"Lee","sequence":"first","affiliation":[{"name":"Department of Chemistry and Biotechnology, Graduate School of Engineering, The University of Tokyo  Tokyo Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yoshihiro","family":"Kaku","sequence":"additional","affiliation":[{"name":"Department of Veterinary Science, National Institute of Infectious Diseases  Tokyo Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Satoshi","family":"Inoue","sequence":"additional","affiliation":[{"name":"Department of Veterinary Science, National Institute of Infectious Diseases  Tokyo Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Teruyuki","family":"Nagamune","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Biotechnology, Graduate School of Engineering, The University of Tokyo  Tokyo Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Masahiro","family":"Kawahara","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Biotechnology, Graduate School of Engineering, The University of Tokyo  Tokyo Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2016,1,14]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-3-540-73259-4_15"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymthe.2005.04.003"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbadis.2008.09.001"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1517\/14712598.7.5.677"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.2174\/092986706776872899"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-61779-974-7_37"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-61779-931-0_2"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.abb.2012.03.009"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymeth.2013.06.010"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/nbt1095-1110"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1093\/protein\/gzr049"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jmb.2008.10.051"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jmb.2003.09.073"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jmb.2007.11.096"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.abb.2012.04.023"},{"key":"e_1_2_7_17_1","first-page":"135","article-title":"Bacterial two hybrid: A versatile one\u2010step intracellular selection method","volume":"911","author":"Pellis M.","year":"2012","journal-title":"Methods Mol. 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