{"id":"https://openalex.org/W3199970584","doi":"https://doi.org/10.1371/journal.pcbi.1008513","title":"Dynamic modelling of the PI3K/MTOR signalling network uncovers biphasic dependence of mTORC1 activity on the mTORC2 subunit SIN1","display_name":"Dynamic modelling of the PI3K/MTOR signalling network uncovers biphasic dependence of mTORC1 activity on the mTORC2 subunit SIN1","publication_year":2021,"publication_date":"2021-09-16","ids":{"openalex":"https://openalex.org/W3199970584","doi":"https://doi.org/10.1371/journal.pcbi.1008513","mag":"3199970584","pmid":"https://pubmed.ncbi.nlm.nih.gov/34529665"},"language":"en","primary_location":{"id":"doi:10.1371/journal.pcbi.1008513","is_oa":true,"landing_page_url":"https://doi.org/10.1371/journal.pcbi.1008513","pdf_url":"https://journals.plos.org/ploscompbiol/article/file?id=10.1371/journal.pcbi.1008513&type=printable","source":{"id":"https://openalex.org/S86033158","display_name":"PLoS Computational Biology","issn_l":"1553-734X","issn":["1553-734X","1553-7358"],"is_oa":true,"is_in_doaj":true,"is_core":true,"host_organization":"https://openalex.org/P4310315706","host_organization_name":"Public Library of Science","host_organization_lineage":["https://openalex.org/P4310315706"],"host_organization_lineage_names":["Public Library of Science"],"type":"journal"},"license":"cc-by","license_id":"https://openalex.org/licenses/cc-by","version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"PLOS Computational Biology","raw_type":"journal-article"},"type":"article","indexed_in":["crossref","doaj","pubmed"],"open_access":{"is_oa":true,"oa_status":"gold","oa_url":"https://journals.plos.org/ploscompbiol/article/file?id=10.1371/journal.pcbi.1008513&type=printable","any_repository_has_fulltext":true},"authorships":[{"author_position":"first","author":{"id":"https://openalex.org/A5013493145","display_name":"Milad Ghomlaghi","orcid":"https://orcid.org/0000-0001-9047-1049"},"institutions":[{"id":"https://openalex.org/I2801239119","display_name":"Australian Regenerative Medicine Institute","ror":"https://ror.org/02qa5kg76","country_code":"AU","type":"facility","lineage":["https://openalex.org/I2801037857","https://openalex.org/I2801239119","https://openalex.org/I56590836"]},{"id":"https://openalex.org/I56590836","display_name":"Monash University","ror":"https://ror.org/02bfwt286","country_code":"AU","type":"education","lineage":["https://openalex.org/I56590836"]}],"countries":["AU"],"is_corresponding":false,"raw_author_name":"Milad Ghomlaghi","raw_affiliation_strings":["Biomedicine Discovery Institute, Monash University, Melbourne, Australia","Department of Biochemistry and Molecular Biology, School of Biomedical Sciences, Monash University, Melbourne, Australia"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Biomedicine Discovery Institute, Monash University, Melbourne, Australia","institution_ids":["https://openalex.org/I2801239119","https://openalex.org/I56590836"]},{"raw_affiliation_string":"Department of Biochemistry and Molecular Biology, School of Biomedical Sciences, Monash University, Melbourne, Australia","institution_ids":["https://openalex.org/I56590836"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5031502585","display_name":"Guang Yang","orcid":"https://orcid.org/0000-0003-4377-1836"},"institutions":[{"id":"https://openalex.org/I129604602","display_name":"The University of Sydney","ror":"https://ror.org/0384j8v12","country_code":"AU","type":"education","lineage":["https://openalex.org/I129604602"]}],"countries":["AU"],"is_corresponding":false,"raw_author_name":"Guang Yang","raw_affiliation_strings":["Charles Perkins Centre, School of Life and Environmental Sciences, The University of Sydney, Sydney, Australia"],"raw_orcid":"https://orcid.org/0000-0003-4377-1836","affiliations":[{"raw_affiliation_string":"Charles Perkins Centre, School of Life and Environmental Sciences, The University of Sydney, Sydney, Australia","institution_ids":["https://openalex.org/I129604602"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5079201651","display_name":"Sung\u2010Young Shin","orcid":"https://orcid.org/0000-0002-1447-9687"},"institutions":[{"id":"https://openalex.org/I2801239119","display_name":"Australian Regenerative Medicine Institute","ror":"https://ror.org/02qa5kg76","country_code":"AU","type":"facility","lineage":["https://openalex.org/I2801037857","https://openalex.org/I2801239119","https://openalex.org/I56590836"]},{"id":"https://openalex.org/I56590836","display_name":"Monash University","ror":"https://ror.org/02bfwt286","country_code":"AU","type":"education","lineage":["https://openalex.org/I56590836"]}],"countries":["AU"],"is_corresponding":false,"raw_author_name":"Sung-Young Shin","raw_affiliation_strings":["Biomedicine Discovery Institute, Monash University, Melbourne, Australia","Department of Biochemistry and Molecular Biology, School of Biomedical Sciences, Monash University, Melbourne, Australia"],"raw_orcid":"https://orcid.org/0000-0002-1447-9687","affiliations":[{"raw_affiliation_string":"Biomedicine Discovery Institute, Monash University, Melbourne, Australia","institution_ids":["https://openalex.org/I2801239119","https://openalex.org/I56590836"]},{"raw_affiliation_string":"Department of Biochemistry and Molecular Biology, School of Biomedical Sciences, Monash University, Melbourne, Australia","institution_ids":["https://openalex.org/I56590836"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5014643889","display_name":"David E. James","orcid":"https://orcid.org/0000-0001-5946-5257"},"institutions":[{"id":"https://openalex.org/I129604602","display_name":"The University of Sydney","ror":"https://ror.org/0384j8v12","country_code":"AU","type":"education","lineage":["https://openalex.org/I129604602"]}],"countries":["AU"],"is_corresponding":false,"raw_author_name":"David E. James","raw_affiliation_strings":["Charles Perkins Centre, School of Life and Environmental Sciences, The University of Sydney, Sydney, Australia"],"raw_orcid":"https://orcid.org/0000-0001-5946-5257","affiliations":[{"raw_affiliation_string":"Charles Perkins Centre, School of Life and Environmental Sciences, The University of Sydney, Sydney, Australia","institution_ids":["https://openalex.org/I129604602"]}]},{"author_position":"last","author":{"id":"https://openalex.org/A5040251521","display_name":"Lan K. Nguyen","orcid":"https://orcid.org/0000-0003-4040-7705"},"institutions":[{"id":"https://openalex.org/I2801239119","display_name":"Australian Regenerative Medicine Institute","ror":"https://ror.org/02qa5kg76","country_code":"AU","type":"facility","lineage":["https://openalex.org/I2801037857","https://openalex.org/I2801239119","https://openalex.org/I56590836"]},{"id":"https://openalex.org/I56590836","display_name":"Monash University","ror":"https://ror.org/02bfwt286","country_code":"AU","type":"education","lineage":["https://openalex.org/I56590836"]}],"countries":["AU"],"is_corresponding":true,"raw_author_name":"Lan K. Nguyen","raw_affiliation_strings":["Biomedicine Discovery Institute, Monash University, Melbourne, Australia","Department of Biochemistry and Molecular Biology, School of Biomedical Sciences, Monash University, Melbourne, Australia"],"raw_orcid":"https://orcid.org/0000-0003-4040-7705","affiliations":[{"raw_affiliation_string":"Biomedicine Discovery Institute, Monash University, Melbourne, Australia","institution_ids":["https://openalex.org/I2801239119","https://openalex.org/I56590836"]},{"raw_affiliation_string":"Department of Biochemistry and Molecular Biology, School of Biomedical Sciences, Monash University, Melbourne, Australia","institution_ids":["https://openalex.org/I56590836"]}]}],"institutions":[],"countries_distinct_count":1,"institutions_distinct_count":5,"corresponding_author_ids":["https://openalex.org/A5040251521"],"corresponding_institution_ids":["https://openalex.org/I2801239119","https://openalex.org/I56590836"],"apc_list":{"value":2655,"currency":"USD","value_usd":2655},"apc_paid":{"value":2655,"currency":"USD","value_usd":2655},"fwci":2.0357,"has_fulltext":true,"cited_by_count":22,"citation_normalized_percentile":{"value":0.87631042,"is_in_top_1_percent":false,"is_in_top_10_percent":false},"cited_by_percentile_year":{"min":89,"max":99},"biblio":{"volume":"17","issue":"9","first_page":"e1008513","last_page":"e1008513"},"is_retracted":false,"is_paratext":false,"is_xpac":false,"primary_topic":{"id":"https://openalex.org/T10952","display_name":"PI3K/AKT/mTOR signaling in cancer","score":0.9998999834060669,"subfield":{"id":"https://openalex.org/subfields/1312","display_name":"Molecular Biology"},"field":{"id":"https://openalex.org/fields/13","display_name":"Biochemistry, Genetics and Molecular Biology"},"domain":{"id":"https://openalex.org/domains/1","display_name":"Life Sciences"}},"topics":[{"id":"https://openalex.org/T10952","display_name":"PI3K/AKT/mTOR signaling in cancer","score":0.9998999834060669,"subfield":{"id":"https://openalex.org/subfields/1312","display_name":"Molecular Biology"},"field":{"id":"https://openalex.org/fields/13","display_name":"Biochemistry, Genetics and Molecular Biology"},"domain":{"id":"https://openalex.org/domains/1","display_name":"Life Sciences"}},{"id":"https://openalex.org/T10497","display_name":"Fungal and yeast genetics research","score":0.9927999973297119,"subfield":{"id":"https://openalex.org/subfields/1312","display_name":"Molecular Biology"},"field":{"id":"https://openalex.org/fields/13","display_name":"Biochemistry, Genetics and Molecular Biology"},"domain":{"id":"https://openalex.org/domains/1","display_name":"Life Sciences"}},{"id":"https://openalex.org/T10169","display_name":"Protein Kinase Regulation and GTPase Signaling","score":0.9908999800682068,"subfield":{"id":"https://openalex.org/subfields/1312","display_name":"Molecular Biology"},"field":{"id":"https://openalex.org/fields/13","display_name":"Biochemistry, Genetics and Molecular Biology"},"domain":{"id":"https://openalex.org/domains/1","display_name":"Life Sciences"}}],"keywords":[{"id":"https://openalex.org/keywords/mtorc2","display_name":"mTORC2","score":0.9412826299667358},{"id":"https://openalex.org/keywords/mtorc1","display_name":"mTORC1","score":0.9352563619613647},{"id":"https://openalex.org/keywords/pi3k/akt/mtor-pathway","display_name":"PI3K/AKT/mTOR pathway","score":0.8242624402046204},{"id":"https://openalex.org/keywords/mechanistic-target-of-rapamycin","display_name":"Mechanistic target of rapamycin","score":0.7304143905639648},{"id":"https://openalex.org/keywords/protein-subunit","display_name":"Protein subunit","score":0.4980452060699463},{"id":"https://openalex.org/keywords/autophagy","display_name":"Autophagy","score":0.4703911542892456},{"id":"https://openalex.org/keywords/computational-biology","display_name":"Computational biology","score":0.4679749310016632},{"id":"https://openalex.org/keywords/biology","display_name":"Biology","score":0.44574394822120667},{"id":"https://openalex.org/keywords/cell-biology","display_name":"Cell biology","score":0.4340583086013794},{"id":"https://openalex.org/keywords/lysosome","display_name":"Lysosome","score":0.41699254512786865},{"id":"https://openalex.org/keywords/chemistry","display_name":"Chemistry","score":0.35390782356262207},{"id":"https://openalex.org/keywords/signal-transduction","display_name":"Signal transduction","score":0.2878569960594177},{"id":"https://openalex.org/keywords/biochemistry","display_name":"Biochemistry","score":0.18444952368736267},{"id":"https://openalex.org/keywords/gene","display_name":"Gene","score":0.117094486951828}],"concepts":[{"id":"https://openalex.org/C107846503","wikidata":"https://www.wikidata.org/wiki/Q14876061","display_name":"mTORC2","level":5,"score":0.9412826299667358},{"id":"https://openalex.org/C98490376","wikidata":"https://www.wikidata.org/wiki/Q14876060","display_name":"mTORC1","level":4,"score":0.9352563619613647},{"id":"https://openalex.org/C86554907","wikidata":"https://www.wikidata.org/wiki/Q285613","display_name":"PI3K/AKT/mTOR pathway","level":3,"score":0.8242624402046204},{"id":"https://openalex.org/C2777949483","wikidata":"https://www.wikidata.org/wiki/Q285613","display_name":"Mechanistic target of rapamycin","level":4,"score":0.7304143905639648},{"id":"https://openalex.org/C104292427","wikidata":"https://www.wikidata.org/wiki/Q899781","display_name":"Protein subunit","level":3,"score":0.4980452060699463},{"id":"https://openalex.org/C203522944","wikidata":"https://www.wikidata.org/wiki/Q288322","display_name":"Autophagy","level":3,"score":0.4703911542892456},{"id":"https://openalex.org/C70721500","wikidata":"https://www.wikidata.org/wiki/Q177005","display_name":"Computational biology","level":1,"score":0.4679749310016632},{"id":"https://openalex.org/C86803240","wikidata":"https://www.wikidata.org/wiki/Q420","display_name":"Biology","level":0,"score":0.44574394822120667},{"id":"https://openalex.org/C95444343","wikidata":"https://www.wikidata.org/wiki/Q7141","display_name":"Cell biology","level":1,"score":0.4340583086013794},{"id":"https://openalex.org/C2780216420","wikidata":"https://www.wikidata.org/wiki/Q83330","display_name":"Lysosome","level":3,"score":0.41699254512786865},{"id":"https://openalex.org/C185592680","wikidata":"https://www.wikidata.org/wiki/Q2329","display_name":"Chemistry","level":0,"score":0.35390782356262207},{"id":"https://openalex.org/C62478195","wikidata":"https://www.wikidata.org/wiki/Q828130","display_name":"Signal transduction","level":2,"score":0.2878569960594177},{"id":"https://openalex.org/C55493867","wikidata":"https://www.wikidata.org/wiki/Q7094","display_name":"Biochemistry","level":1,"score":0.18444952368736267},{"id":"https://openalex.org/C104317684","wikidata":"https://www.wikidata.org/wiki/Q7187","display_name":"Gene","level":2,"score":0.117094486951828},{"id":"https://openalex.org/C190283241","wikidata":"https://www.wikidata.org/wiki/Q14599311","display_name":"Apoptosis","level":2,"score":0.0},{"id":"https://openalex.org/C181199279","wikidata":"https://www.wikidata.org/wiki/Q8047","display_name":"Enzyme","level":2,"score":0.0}],"mesh":[{"descriptor_ui":"D000076222","descriptor_name":"Mechanistic Target of Rapamycin Complex 1","qualifier_ui":"Q000378","qualifier_name":"metabolism","is_major_topic":false},{"descriptor_ui":"D000076222","descriptor_name":"Mechanistic Target of Rapamycin Complex 1","qualifier_ui":"Q000378","qualifier_name":"metabolism","is_major_topic":false},{"descriptor_ui":"D000076222","descriptor_name":"Mechanistic Target of Rapamycin Complex 1","qualifier_ui":"Q000378","qualifier_name":"metabolism","is_major_topic":false},{"descriptor_ui":"D000076222","descriptor_name":"Mechanistic Target of Rapamycin Complex 1","qualifier_ui":"Q000378","qualifier_name":"metabolism","is_major_topic":false},{"descriptor_ui":"D000076225","descriptor_name":"Mechanistic Target of Rapamycin Complex 2","qualifier_ui":"Q000378","qualifier_name":"metabolism","is_major_topic":false},{"descriptor_ui":"D000076225","descriptor_name":"Mechanistic Target of Rapamycin Complex 2","qualifier_ui":"Q000378","qualifier_name":"metabolism","is_major_topic":false},{"descriptor_ui":"D000076225","descriptor_name":"Mechanistic Target of Rapamycin Complex 2","qualifier_ui":"Q000378","qualifier_name":"metabolism","is_major_topic":false},{"descriptor_ui":"D000076225","descriptor_name":"Mechanistic Target of Rapamycin Complex 2","qualifier_ui":"Q000378","qualifier_name":"metabolism","is_major_topic":false},{"descriptor_ui":"D000076225","descriptor_name":"Mechanistic Target of Rapamycin Complex 2","qualifier_ui":"Q000737","qualifier_name":"chemistry","is_major_topic":false},{"descriptor_ui":"D000076225","descriptor_name":"Mechanistic Target of Rapamycin Complex 2","qualifier_ui":"Q000737","qualifier_name":"chemistry","is_major_topic":false},{"descriptor_ui":"D000076225","descriptor_name":"Mechanistic Target of Rapamycin Complex 2","qualifier_ui":"Q000737","qualifier_name":"chemistry","is_major_topic":false},{"descriptor_ui":"D000076225","descriptor_name":"Mechanistic Target of Rapamycin Complex 2","qualifier_ui":"Q000737","qualifier_name":"chemistry","is_major_topic":false},{"descriptor_ui":"D000076242","descriptor_name":"mTOR Associated Protein, LST8 Homolog","qualifier_ui":"Q000378","qualifier_name":"metabolism","is_major_topic":false},{"descriptor_ui":"D000076242","descriptor_name":"mTOR Associated Protein, LST8 Homolog","qualifier_ui":"Q000378","qualifier_name":"metabolism","is_major_topic":false},{"descriptor_ui":"D000076242","descriptor_name":"mTOR Associated Protein, LST8 Homolog","qualifier_ui":"Q000378","qualifier_name":"metabolism","is_major_topic":false},{"descriptor_ui":"D000076242","descriptor_name":"mTOR Associated Protein, LST8 Homolog","qualifier_ui":"Q000378","qualifier_name":"metabolism","is_major_topic":false},{"descriptor_ui":"D000818","descriptor_name":"Animals","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D000818","descriptor_name":"Animals","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D000818","descriptor_name":"Animals","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D000818","descriptor_name":"Animals","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D002460","descriptor_name":"Cell Line","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D002460","descriptor_name":"Cell Line","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D002460","descriptor_name":"Cell Line","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D002460","descriptor_name":"Cell Line","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D015203","descriptor_name":"Reproducibility of Results","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D015203","descriptor_name":"Reproducibility of Results","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D015203","descriptor_name":"Reproducibility of Results","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D015203","descriptor_name":"Reproducibility of Results","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D015398","descriptor_name":"Signal Transduction","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D015398","descriptor_name":"Signal Transduction","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D015398","descriptor_name":"Signal Transduction","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D015398","descriptor_name":"Signal Transduction","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D019869","descriptor_name":"Phosphatidylinositol 3-Kinases","qualifier_ui":"Q000378","qualifier_name":"metabolism","is_major_topic":false},{"descriptor_ui":"D019869","descriptor_name":"Phosphatidylinositol 3-Kinases","qualifier_ui":"Q000378","qualifier_name":"metabolism","is_major_topic":false},{"descriptor_ui":"D019869","descriptor_name":"Phosphatidylinositol 3-Kinases","qualifier_ui":"Q000378","qualifier_name":"metabolism","is_major_topic":false},{"descriptor_ui":"D019869","descriptor_name":"Phosphatidylinositol 3-Kinases","qualifier_ui":"Q000378","qualifier_name":"metabolism","is_major_topic":false},{"descriptor_ui":"D047908","descriptor_name":"Intracellular Signaling Peptides and Proteins","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D047908","descriptor_name":"Intracellular Signaling Peptides and Proteins","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D047908","descriptor_name":"Intracellular Signaling Peptides and Proteins","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D047908","descriptor_name":"Intracellular Signaling Peptides and Proteins","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D058570","descriptor_name":"TOR Serine-Threonine Kinases","qualifier_ui":"Q000378","qualifier_name":"metabolism","is_major_topic":false},{"descriptor_ui":"D058570","descriptor_name":"TOR Serine-Threonine Kinases","qualifier_ui":"Q000378","qualifier_name":"metabolism","is_major_topic":false},{"descriptor_ui":"D058570","descriptor_name":"TOR Serine-Threonine Kinases","qualifier_ui":"Q000378","qualifier_name":"metabolism","is_major_topic":false},{"descriptor_ui":"D058570","descriptor_name":"TOR Serine-Threonine Kinases","qualifier_ui":"Q000378","qualifier_name":"metabolism","is_major_topic":false}],"locations_count":5,"locations":[{"id":"doi:10.1371/journal.pcbi.1008513","is_oa":true,"landing_page_url":"https://doi.org/10.1371/journal.pcbi.1008513","pdf_url":"https://journals.plos.org/ploscompbiol/article/file?id=10.1371/journal.pcbi.1008513&type=printable","source":{"id":"https://openalex.org/S86033158","display_name":"PLoS Computational Biology","issn_l":"1553-734X","issn":["1553-734X","1553-7358"],"is_oa":true,"is_in_doaj":true,"is_core":true,"host_organization":"https://openalex.org/P4310315706","host_organization_name":"Public Library of Science","host_organization_lineage":["https://openalex.org/P4310315706"],"host_organization_lineage_names":["Public Library of Science"],"type":"journal"},"license":"cc-by","license_id":"https://openalex.org/licenses/cc-by","version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"PLOS Computational Biology","raw_type":"journal-article"},{"id":"pmid:34529665","is_oa":false,"landing_page_url":"https://pubmed.ncbi.nlm.nih.gov/34529665","pdf_url":null,"source":{"id":"https://openalex.org/S4306525036","display_name":"PubMed","issn_l":null,"issn":null,"is_oa":false,"is_in_doaj":false,"is_core":false,"host_organization":"https://openalex.org/I1299303238","host_organization_name":"National Institutes of Health","host_organization_lineage":["https://openalex.org/I1299303238"],"host_organization_lineage_names":[],"type":"repository"},"license":null,"license_id":null,"version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"PLoS computational biology","raw_type":null},{"id":"pmh:oai:doaj.org/article:712302b6419c4aefa8ed03c345a6d2de","is_oa":true,"landing_page_url":"https://doaj.org/article/712302b6419c4aefa8ed03c345a6d2de","pdf_url":null,"source":{"id":"https://openalex.org/S4306401280","display_name":"DOAJ (DOAJ: Directory of Open Access Journals)","issn_l":null,"issn":null,"is_oa":false,"is_in_doaj":false,"is_core":false,"host_organization":null,"host_organization_name":null,"host_organization_lineage":[],"host_organization_lineage_names":[],"type":"repository"},"license":"cc-by-sa","license_id":"https://openalex.org/licenses/cc-by-sa","version":"submittedVersion","is_accepted":false,"is_published":false,"raw_source_name":"PLoS Computational Biology, Vol 17, Iss 9, p e1008513 (2021)","raw_type":"article"},{"id":"pmh:oai:europepmc.org:7368314","is_oa":true,"landing_page_url":"http://europepmc.org/pmc/articles/PMC8478217","pdf_url":null,"source":{"id":"https://openalex.org/S4306400806","display_name":"Europe PMC (PubMed Central)","issn_l":null,"issn":null,"is_oa":false,"is_in_doaj":false,"is_core":false,"host_organization":"https://openalex.org/I1303153112","host_organization_name":"European Bioinformatics Institute","host_organization_lineage":["https://openalex.org/I1303153112"],"host_organization_lineage_names":[],"type":"repository"},"license":"other-oa","license_id":"https://openalex.org/licenses/other-oa","version":"submittedVersion","is_accepted":false,"is_published":false,"raw_source_name":"","raw_type":"Text"},{"id":"pmh:oai:pubmedcentral.nih.gov:8478217","is_oa":true,"landing_page_url":"https://www.ncbi.nlm.nih.gov/pmc/articles/8478217","pdf_url":null,"source":{"id":"https://openalex.org/S2764455111","display_name":"PubMed Central","issn_l":null,"issn":null,"is_oa":true,"is_in_doaj":false,"is_core":false,"host_organization":"https://openalex.org/I1299303238","host_organization_name":"National Institutes of Health","host_organization_lineage":["https://openalex.org/I1299303238"],"host_organization_lineage_names":[],"type":"repository"},"license":"cc-by","license_id":"https://openalex.org/licenses/cc-by","version":"submittedVersion","is_accepted":false,"is_published":false,"raw_source_name":"PLoS Comput Biol","raw_type":"Text"}],"best_oa_location":{"id":"doi:10.1371/journal.pcbi.1008513","is_oa":true,"landing_page_url":"https://doi.org/10.1371/journal.pcbi.1008513","pdf_url":"https://journals.plos.org/ploscompbiol/article/file?id=10.1371/journal.pcbi.1008513&type=printable","source":{"id":"https://openalex.org/S86033158","display_name":"PLoS Computational Biology","issn_l":"1553-734X","issn":["1553-734X","1553-7358"],"is_oa":true,"is_in_doaj":true,"is_core":true,"host_organization":"https://openalex.org/P4310315706","host_organization_name":"Public Library of Science","host_organization_lineage":["https://openalex.org/P4310315706"],"host_organization_lineage_names":["Public Library of Science"],"type":"journal"},"license":"cc-by","license_id":"https://openalex.org/licenses/cc-by","version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"PLOS Computational Biology","raw_type":"journal-article"},"sustainable_development_goals":[{"score":0.6299999952316284,"display_name":"Good health and well-being","id":"https://metadata.un.org/sdg/3"}],"awards":[{"id":"https://openalex.org/G1827032085","display_name":null,"funder_award_id":"IIRS-20-094","funder_id":"https://openalex.org/F4320320438","funder_display_name":"National Breast Cancer Foundation"},{"id":"https://openalex.org/G803385416","display_name":null,"funder_award_id":"MCRF18026","funder_id":"https://openalex.org/F4320310187","funder_display_name":"Victorian Cancer Agency"}],"funders":[{"id":"https://openalex.org/F4320310187","display_name":"Victorian Cancer Agency","ror":"https://ror.org/0316wrd42"},{"id":"https://openalex.org/F4320312903","display_name":"Marshfield Clinic Research Foundation","ror":null},{"id":"https://openalex.org/F4320320438","display_name":"National Breast Cancer Foundation","ror":"https://ror.org/0120ky124"},{"id":"https://openalex.org/F4320334707","display_name":"Cancer Council Victoria","ror":"https://ror.org/023m51b03"}],"has_content":{"pdf":true,"grobid_xml":true},"content_urls":{"pdf":"https://content.openalex.org/works/W3199970584.pdf","grobid_xml":"https://content.openalex.org/works/W3199970584.grobid-xml"},"referenced_works_count":49,"referenced_works":["https://openalex.org/W1861089690","https://openalex.org/W1930038475","https://openalex.org/W1971703620","https://openalex.org/W1993517337","https://openalex.org/W2000731858","https://openalex.org/W2006559495","https://openalex.org/W2021012077","https://openalex.org/W2038874082","https://openalex.org/W2043851046","https://openalex.org/W2065887259","https://openalex.org/W2071333117","https://openalex.org/W2078250780","https://openalex.org/W2084346552","https://openalex.org/W2094399892","https://openalex.org/W2096248361","https://openalex.org/W2096561460","https://openalex.org/W2097492375","https://openalex.org/W2099540110","https://openalex.org/W2100486339","https://openalex.org/W2101771026","https://openalex.org/W2102424174","https://openalex.org/W2111352469","https://openalex.org/W2112739348","https://openalex.org/W2113491029","https://openalex.org/W2117028091","https://openalex.org/W2128551987","https://openalex.org/W2144059623","https://openalex.org/W2152289580","https://openalex.org/W2154731971","https://openalex.org/W2155763709","https://openalex.org/W2375577403","https://openalex.org/W2502719767","https://openalex.org/W2535462468","https://openalex.org/W2550846703","https://openalex.org/W2565099035","https://openalex.org/W2586394106","https://openalex.org/W2588384647","https://openalex.org/W2596495711","https://openalex.org/W2612937617","https://openalex.org/W2765866710","https://openalex.org/W2784207779","https://openalex.org/W2913758221","https://openalex.org/W2945448086","https://openalex.org/W2976828099","https://openalex.org/W3001475835","https://openalex.org/W3013884756","https://openalex.org/W3126828074","https://openalex.org/W4238567307","https://openalex.org/W6940447674"],"related_works":["https://openalex.org/W2078821200","https://openalex.org/W2131978771","https://openalex.org/W3132255180","https://openalex.org/W3199970584","https://openalex.org/W2885215830","https://openalex.org/W1597855498","https://openalex.org/W2550775385","https://openalex.org/W2102328908","https://openalex.org/W2054117275","https://openalex.org/W1487550568"],"abstract_inverted_index":{"The":[0,18],"PI3K/MTOR":[1,117,227],"signalling":[2,228],"network":[3,86,100],"regulates":[4],"a":[5,27,148,211,222,235],"broad":[6],"array":[7],"of":[8,21,115,154,180,198,226],"critical":[9,126],"cellular":[10],"processes,":[11],"including":[12,47,129],"cell":[13],"growth,":[14],"metabolism":[15],"and":[16,34,39,53,60,63,67,92,105,135,204,207,233,241],"autophagy.":[17],"mechanistic":[19,122,127,224],"target":[20,214],"rapamycin":[22],"(MTOR)":[23],"kinase":[24],"functions":[25],"as":[26,51,210],"core":[28],"catalytic":[29],"subunit":[30,161],"in":[31,81,102,169,200,215],"two":[32],"physically":[33],"functionally":[35,71],"distinct":[36],"complexes":[37],"mTORC1":[38,59,155,203,240],"mTORC2,":[40],"which":[41,163,182],"also":[42],"share":[43],"other":[44],"common":[45],"components":[46],"MLST8":[48,133,199,209],"(also":[49],"known":[50],"G\u03b2L)":[52],"DEPTOR.":[54],"Despite":[55],"intensive":[56],"research,":[57],"how":[58,68],"2":[61],"assembly":[62],"activity":[64,156,206],"are":[65,70],"coordinated,":[66],"they":[69],"linked":[72],"remain":[73],"to":[74,83,109],"be":[75],"fully":[76],"characterized.":[77],"This":[78],"is":[79,164,183,187],"due":[80],"part":[82],"the":[84,111,116,136,158,195],"complex":[85],"wiring,":[87],"featuring":[88],"multiple":[89],"feedback":[90,139],"loops":[91],"intricate":[93],"post-translational":[94],"modifications.":[95],"Here,":[96],"we":[97],"integrate":[98],"predictive":[99],"modelling,":[101],"vitro":[103],"experiments":[104],"-omics":[106],"data":[107],"analysis":[108,176],"elucidate":[110],"emergent":[112],"dynamic":[113],"behaviour":[114],"network.":[118],"We":[119],"construct":[120],"new":[121,223],"models":[123],"that":[124,178],"encapsulate":[125],"details,":[128],"mTORC1/2":[130,231],"coordination":[131],"by":[132,144,185,189],"(de)ubiquitination":[134],"Akt-to-mTORC2":[137],"positive":[138],"loop.":[140],"Model":[141],"simulations":[142],"validated":[143],"experimental":[145],"studies":[146],"revealed":[147],"previously":[149],"unknown":[150],"biphasic,":[151],"threshold-gated":[152],"dependence":[153],"on":[157],"key":[159],"mTORC2":[160],"SIN1,":[162],"robust":[165],"against":[166],"cell-to-cell":[167],"variation":[168],"protein":[170],"expression.":[171],"In":[172],"addition,":[173],"our":[174,219],"integrative":[175],"demonstrates":[177],"ubiquitination":[179],"MLST8,":[181],"reversed":[184],"OTUD7B,":[186],"regulated":[188],"IRS1/2.":[190],"Our":[191],"results":[192],"further":[193],"support":[194],"essential":[196],"role":[197],"enabling":[201],"both":[202],"2's":[205],"suggest":[208],"viable":[212],"therapeutic":[213],"breast":[216],"cancer.":[217],"Overall,":[218],"study":[220],"reports":[221],"model":[225],"incorporating":[229],"MLST8-mediated":[230],"formation":[232],"unveils":[234],"novel":[236],"regulatory":[237],"linkage":[238],"between":[239],"mTORC2.":[242]},"counts_by_year":[{"year":2025,"cited_by_count":1},{"year":2024,"cited_by_count":9},{"year":2023,"cited_by_count":7},{"year":2022,"cited_by_count":4},{"year":2021,"cited_by_count":1}],"updated_date":"2026-05-06T08:25:59.206177","created_date":"2025-10-10T00:00:00"}