{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T11:23:55Z","timestamp":1791113035232,"version":"4.1.0"},"reference-count":105,"publisher":"American Association for the Advancement of Science (AAAS)","issue":"217","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Sci. Signal."],"published-print":{"date-parts":[[2012,3,27]]},"abstract":"<jats:p>Modeling and testing network structures reveal a distinct mechanism of mTORC2 activation by insulin.<\/jats:p>","DOI":"10.1126\/scisignal.2002469","type":"journal-article","created":{"date-parts":[[2012,3,27]],"date-time":"2012-03-27T22:15:23Z","timestamp":1332886523000},"source":"Crossref","is-referenced-by-count":66,"title":["A Dynamic Network Model of mTOR Signaling Reveals TSC-Independent mTORC2 Regulation"],"prefix":"10.1126","volume":"5","author":[{"given":"Piero","family":"Dalle Pezze","sequence":"first","affiliation":[{"name":"Institute for Ageing and Health, Newcastle University, Campus for Ageing and Vitality, Newcastle upon Tyne NE4 5PL, UK."},{"name":"Centre for Integrated Systems Biology of Ageing and Nutrition, Institute for Ageing and Health, Newcastle University, Newcastle upon Tyne NE4 5PL, UK."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annika G.","family":"Sonntag","sequence":"additional","affiliation":[{"name":"Bioinformatics and Molecular Genetics (Faculty of Biology), Albert-Ludwigs-Universit\u00e4t Freiburg, 79104 Freiburg, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antje","family":"Thien","sequence":"additional","affiliation":[{"name":"Renal Division, University Hospital Freiburg, 79106 Freiburg, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mirja T.","family":"Prentzell","sequence":"additional","affiliation":[{"name":"Bioinformatics and Molecular Genetics (Faculty of Biology), Albert-Ludwigs-Universit\u00e4t Freiburg, 79104 Freiburg, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Markus","family":"G\u00f6del","sequence":"additional","affiliation":[{"name":"Renal Division, University Hospital Freiburg, 79106 Freiburg, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sven","family":"Fischer","sequence":"additional","affiliation":[{"name":"Bioinformatics and Molecular Genetics (Faculty of Biology), Albert-Ludwigs-Universit\u00e4t Freiburg, 79104 Freiburg, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elke","family":"Neumann-Haefelin","sequence":"additional","affiliation":[{"name":"Renal Division, University Hospital Freiburg, 79106 Freiburg, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tobias B.","family":"Huber","sequence":"additional","affiliation":[{"name":"Renal Division, University Hospital Freiburg, 79106 Freiburg, Germany."},{"name":"BIOSS Centre for Biological Signalling Studies, Albert-Ludwigs-Universit\u00e4t Freiburg, 79104 Freiburg, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ralf","family":"Baumeister","sequence":"additional","affiliation":[{"name":"Bioinformatics and Molecular Genetics (Faculty of Biology), Albert-Ludwigs-Universit\u00e4t Freiburg, 79104 Freiburg, Germany."},{"name":"BIOSS Centre for Biological Signalling Studies, Albert-Ludwigs-Universit\u00e4t Freiburg, 79104 Freiburg, Germany."},{"name":"Center for Systems Biology (ZBSA), Albert-Ludwigs-Universit\u00e4t Freiburg, 79104 Freiburg, Germany."},{"name":"ZBMZ (Faculty of Medicine) and Freiburg Institute for Advanced Studies (FRIAS), Albert-Ludwigs-Universit\u00e4t Freiburg, 79104 Freiburg, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daryl P.","family":"Shanley","sequence":"additional","affiliation":[{"name":"Institute for Ageing and Health, Newcastle University, Campus for Ageing and Vitality, Newcastle upon Tyne NE4 5PL, UK."},{"name":"Centre for Integrated Systems Biology of Ageing and Nutrition, Institute for Ageing and Health, Newcastle University, Newcastle upon Tyne NE4 5PL, UK."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kathrin","family":"Thedieck","sequence":"additional","affiliation":[{"name":"Bioinformatics and Molecular Genetics (Faculty of Biology), Albert-Ludwigs-Universit\u00e4t Freiburg, 79104 Freiburg, Germany."},{"name":"BIOSS Centre for Biological Signalling Studies, Albert-Ludwigs-Universit\u00e4t Freiburg, 79104 Freiburg, Germany."},{"name":"Center for Systems Biology (ZBSA), Albert-Ludwigs-Universit\u00e4t Freiburg, 79104 Freiburg, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"221","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrm3025"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.tem.2010.12.003"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1042\/BST0390451"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ceb.2009.01.024"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.tibs.2009.09.004"},{"key":"e_1_3_2_7_2","first-page":"241","article-title":"New inhibitors of the PI3K-Akt-mTOR pathway: Insights into mTOR signaling from a new generation of Tor kinase domain inhibitors (TORKinibs)","volume":"347","author":"Feldman M. E.","year":"2010","unstructured":"Feldman M. E., Shokat K. M., New inhibitors of the PI3K-Akt-mTOR pathway: Insights into mTOR signaling from a new generation of Tor kinase domain inhibitors (TORKinibs). Curr. Top. Microbiol. Immunol. 347, 241\u2013262 (2010).","journal-title":"Curr. Top. Microbiol. Immunol."},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2010.09.026"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2010.02.024"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1042\/BST0370289"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1042\/BST0370223"},{"key":"e_1_3_2_12_2","doi-asserted-by":"crossref","unstructured":"K. Thedieck M. N. Hall in The Handbook of Cell Signaling R. Bradshaw E. Dennis Eds. (Elsevier San Diego CA 2009) vol. 3 chap. 274 pp. 2285\u20132293.","DOI":"10.1016\/B978-0-12-374145-5.00274-6"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1038\/ncb1547"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0001217"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2007.03.003"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M702376200"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M704406200"},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M702636200"},{"key":"e_1_3_2_19_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M800723200"},{"key":"e_1_3_2_20_2","doi-asserted-by":"publisher","DOI":"10.1038\/ncb1183"},{"key":"e_1_3_2_21_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M110.166991"},{"key":"e_1_3_2_22_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1106148"},{"key":"e_1_3_2_23_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2006.08.033"},{"key":"e_1_3_2_24_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.devcel.2006.08.013"},{"key":"e_1_3_2_25_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M508361200"},{"key":"e_1_3_2_26_2","doi-asserted-by":"publisher","DOI":"10.1042\/BJ20081668"},{"key":"e_1_3_2_27_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cub.2004.06.054"},{"key":"e_1_3_2_28_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrm2822"},{"key":"e_1_3_2_29_2","doi-asserted-by":"publisher","DOI":"10.1042\/BJ20071518"},{"key":"e_1_3_2_30_2","first-page":"31","article-title":"Protein kinase B (PKB\/Akt), a key mediator of the PI3K signaling pathway","volume":"346","author":"Fayard E.","year":"2010","unstructured":"Fayard E., Xue G., Parcellier A., Bozulic L., Hemmings B. A., Protein kinase B (PKB\/Akt), a key mediator of the PI3K signaling pathway. Curr. Top. Microbiol. Immunol. 346, 31\u201356 (2010).","journal-title":"Curr. Top. Microbiol. Immunol."},{"key":"e_1_3_2_31_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng1494"},{"key":"e_1_3_2_32_2","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.00289-08"},{"key":"e_1_3_2_33_2","doi-asserted-by":"publisher","DOI":"10.1042\/BST0370217"},{"key":"e_1_3_2_34_2","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-09-0975"},{"key":"e_1_3_2_35_2","doi-asserted-by":"publisher","DOI":"10.1038\/onc.2010.630"},{"key":"e_1_3_2_36_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0602282103"},{"key":"e_1_3_2_37_2","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.01061-10"},{"key":"e_1_3_2_38_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cub.2008.06.068"},{"key":"e_1_3_2_39_2","doi-asserted-by":"publisher","DOI":"10.1091\/mbc.e10-01-0009"},{"key":"e_1_3_2_40_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.devcel.2010.03.017"},{"key":"e_1_3_2_41_2","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.201001129"},{"key":"e_1_3_2_42_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI117401"},{"key":"e_1_3_2_43_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.272.37.23448"},{"key":"e_1_3_2_44_2","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.25.16.7239-7248.2005"},{"key":"e_1_3_2_45_2","doi-asserted-by":"publisher","DOI":"10.1038\/msb.2010.108"},{"key":"e_1_3_2_46_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pcbi.1000287"},{"key":"e_1_3_2_47_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M110.106849"},{"key":"e_1_3_2_48_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pcbi.1000005"},{"key":"e_1_3_2_49_2","doi-asserted-by":"publisher","DOI":"10.1038\/msb.2009.19"},{"key":"e_1_3_2_50_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pcbi.1000096"},{"key":"e_1_3_2_51_2","doi-asserted-by":"publisher","DOI":"10.1038\/msb.2008.78"},{"key":"e_1_3_2_52_2","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-09-0777"},{"key":"e_1_3_2_53_2","doi-asserted-by":"publisher","DOI":"10.1038\/nbt1330"},{"key":"e_1_3_2_54_2","doi-asserted-by":"publisher","DOI":"10.1038\/msb.2008.53"},{"key":"e_1_3_2_55_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajpendo.00571.2001"},{"key":"e_1_3_2_56_2","first-page":"2683","article-title":"Computational analysis of mTOR signaling pathway: Bifurcation, carcinogenesis, and drug discovery","volume":"30","author":"Wang G.","year":"2010","unstructured":"Wang G., Krueger G. R., Computational analysis of mTOR signaling pathway: Bifurcation, carcinogenesis, and drug discovery. Anticancer Res. 30, 2683\u20132688 (2010).","journal-title":"Anticancer Res."},{"key":"e_1_3_2_57_2","doi-asserted-by":"publisher","DOI":"10.1039\/b816965a"},{"key":"e_1_3_2_58_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0011092"},{"key":"e_1_3_2_59_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrm1570"},{"key":"e_1_3_2_60_2","doi-asserted-by":"publisher","DOI":"10.1038\/nbt.1558"},{"key":"e_1_3_2_61_2","doi-asserted-by":"publisher","DOI":"10.3109\/08977194.2010.518616"},{"key":"e_1_3_2_62_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.275.10.7416"},{"key":"e_1_3_2_63_2","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.01665-08"},{"key":"e_1_3_2_64_2","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-08-3014"},{"key":"e_1_3_2_65_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M109.096222"},{"key":"e_1_3_2_66_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pbio.1000038"},{"key":"e_1_3_2_67_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M900301200"},{"key":"e_1_3_2_68_2","doi-asserted-by":"publisher","DOI":"10.4161\/auto.5.5.8504"},{"key":"e_1_3_2_69_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jim.2009.03.018"},{"key":"e_1_3_2_70_2","doi-asserted-by":"publisher","DOI":"10.1101\/gad.1945410"},{"key":"e_1_3_2_71_2","doi-asserted-by":"publisher","DOI":"10.1101\/gr.1262503"},{"key":"e_1_3_2_72_2","doi-asserted-by":"publisher","DOI":"10.1186\/1752-0509-5-14"},{"key":"e_1_3_2_73_2","doi-asserted-by":"publisher","DOI":"10.1002\/j.1460-2075.1996.tb00911.x"},{"key":"e_1_3_2_74_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.273.36.23534"},{"key":"e_1_3_2_75_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.271.36.21920"},{"key":"e_1_3_2_76_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrm1838"},{"key":"e_1_3_2_77_2","doi-asserted-by":"publisher","DOI":"10.1038\/35018085"},{"key":"e_1_3_2_78_2","doi-asserted-by":"publisher","DOI":"10.1126\/scisignal.2000517"},{"key":"e_1_3_2_79_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2008.02.024"},{"key":"e_1_3_2_80_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M406731200"},{"key":"e_1_3_2_81_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M303083200"},{"key":"e_1_3_2_82_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M410344200"},{"key":"e_1_3_2_83_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M005953200"},{"key":"e_1_3_2_84_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M408797200"},{"key":"e_1_3_2_85_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cellsig.2004.01.008"},{"key":"e_1_3_2_86_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.yjmcc.2007.10.016"},{"key":"e_1_3_2_87_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.275.12.8271"},{"key":"e_1_3_2_88_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1199484"},{"key":"e_1_3_2_89_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1199498"},{"key":"e_1_3_2_90_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0960-9822(00)00441-3"},{"key":"e_1_3_2_91_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M110.195016"},{"key":"e_1_3_2_92_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2011.02.014"},{"key":"e_1_3_2_93_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(19)61974-5"},{"key":"e_1_3_2_94_2","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.19.10.7203"},{"key":"e_1_3_2_95_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(17)42304-0"},{"key":"e_1_3_2_96_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrm2882"},{"key":"e_1_3_2_97_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.77.16.8957-8951.2003"},{"key":"e_1_3_2_98_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1478-5382(03)02370-9"},{"key":"e_1_3_2_99_2","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btl485"},{"key":"e_1_3_2_100_2","doi-asserted-by":"publisher","DOI":"10.1145\/29380.29864"},{"key":"e_1_3_2_101_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.220.4598.671"},{"key":"e_1_3_2_102_2","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/bti799"},{"key":"e_1_3_2_103_2","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btl111"},{"key":"e_1_3_2_104_2","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btg015"},{"key":"e_1_3_2_105_2","unstructured":"R Development Core Team R: A Language and Environment for Statistical Computing (R Foundation for Statistical Computing Vienna Austria 2005) Version 2.12.1."},{"key":"e_1_3_2_106_2","doi-asserted-by":"publisher","DOI":"10.1109\/TAC.1974.1100705"}],"container-title":["Science Signaling"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.science.org\/doi\/pdf\/10.1126\/scisignal.2002469","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,1,16]],"date-time":"2024-01-16T10:46:16Z","timestamp":1705401976000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.science.org\/doi\/10.1126\/scisignal.2002469"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2012,3,27]]},"references-count":105,"journal-issue":{"issue":"217","published-print":{"date-parts":[[2012,3,27]]}},"alternative-id":["10.1126\/scisignal.2002469"],"URL":"https:\/\/doi.org\/10.1126\/scisignal.2002469","relation":{},"ISSN":["1945-0877","1937-9145"],"issn-type":[{"value":"1945-0877","type":"print"},{"value":"1937-9145","type":"electronic"}],"subject":[],"published":{"date-parts":[[2012,3,27]]}}}