{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,16]],"date-time":"2026-04-16T06:34:11Z","timestamp":1776321251381,"version":"3.50.1"},"update-to":[{"DOI":"10.1371\/journal.pcbi.1010690","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2023,4,11]],"date-time":"2023-04-11T00:00:00Z","timestamp":1681171200000}}],"reference-count":81,"publisher":"Public Library of Science (PLoS)","issue":"3","license":[{"start":{"date-parts":[[2023,3,30]],"date-time":"2023-03-30T00:00:00Z","timestamp":1680134400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"NIH","award":["U54 RFA-HG-14-001"],"award-info":[{"award-number":["U54 RFA-HG-14-001"]}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","award":["R15DE028434"],"award-info":[{"award-number":["R15DE028434"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]},{"name":"NIH","award":["R35GM141873"],"award-info":[{"award-number":["R35GM141873"]}]},{"DOI":"10.13039\/100005567","name":"H. Lee Moffitt Cancer Center and Research Institute","doi-asserted-by":"publisher","award":["Moffitt Innovative Core Project"],"award-info":[{"award-number":["Moffitt Innovative Core Project"]}],"id":[{"id":"10.13039\/100005567","id-type":"DOI","asserted-by":"publisher"}]},{"name":"NCI","award":["P30-CA076292"],"award-info":[{"award-number":["P30-CA076292"]}]}],"content-domain":{"domain":["www.ploscompbiol.org"],"crossmark-restriction":false},"short-container-title":["PLoS Comput Biol"],"abstract":"<jats:p>We analyzed large-scale post-translational modification (PTM) data to outline cell signaling pathways affected by tyrosine kinase inhibitors (TKIs) in ten lung cancer cell lines. Tyrosine phosphorylated, lysine ubiquitinated, and lysine acetylated proteins were concomitantly identified using sequential enrichment of post translational modification (SEPTM) proteomics. Machine learning was used to identify PTM clusters that represent functional modules that respond to TKIs. To model lung cancer signaling at the protein level, PTM clusters were used to create a co-cluster correlation network (CCCN) and select protein-protein interactions (PPIs) from a large network of curated PPIs to create a cluster-filtered network (CFN). Next, we constructed a Pathway Crosstalk Network (PCN) by connecting pathways from NCATS BioPlanet whose member proteins have PTMs that co-cluster. Interrogating the CCCN, CFN, and PCN individually and in combination yields insights into the response of lung cancer cells to TKIs. We highlight examples where cell signaling pathways involving EGFR and ALK exhibit crosstalk with BioPlanet pathways: Transmembrane transport of small molecules; and Glycolysis and gluconeogenesis. These data identify known and previously unappreciated connections between receptor tyrosine kinase (RTK) signal transduction and oncogenic metabolic reprogramming in lung cancer. Comparison to a CFN generated from a previous multi-PTM analysis of lung cancer cell lines reveals a common core of PPIs involving heat shock\/chaperone proteins, metabolic enzymes, cytoskeletal components, and RNA-binding proteins. Elucidation of points of crosstalk among signaling pathways employing different PTMs reveals new potential drug targets and candidates for synergistic attack through combination drug therapy.<\/jats:p>","DOI":"10.1371\/journal.pcbi.1010690","type":"journal-article","created":{"date-parts":[[2023,3,30]],"date-time":"2023-03-30T13:56:32Z","timestamp":1680184592000},"page":"e1010690","update-policy":"https:\/\/doi.org\/10.1371\/journal.pcbi.corrections_policy","source":"Crossref","is-referenced-by-count":18,"title":["Network models of protein phosphorylation, acetylation, and ubiquitination connect metabolic and cell signaling pathways in lung cancer"],"prefix":"10.1371","volume":"19","author":[{"given":"Karen E.","family":"Ross","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Guolin","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cuneyt","family":"Akcora","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yu","family":"Lin","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bin","family":"Fang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3818-1762","authenticated-orcid":true,"given":"John","family":"Koomen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eric B.","family":"Haura","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2673-5892","authenticated-orcid":true,"given":"Mark","family":"Grimes","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"340","published-online":{"date-parts":[[2023,3,30]]},"reference":[{"issue":"6","key":"pcbi.1010690.ref001","doi-asserted-by":"crossref","first-page":"666","DOI":"10.1038\/nsmb.1842","article-title":"Post-translational modifications in signal integration","volume":"17","author":"YL Deribe","year":"2010","journal-title":"Nat Struct Mol Biol"},{"key":"pcbi.1010690.ref002","doi-asserted-by":"crossref","first-page":"599","DOI":"10.1038\/msb.2012.31","article-title":"Deciphering a global network of functionally associated post-translational modifications","volume":"8","author":"P Minguez","year":"2012","journal-title":"Mol Syst Biol"},{"issue":"2","key":"pcbi.1010690.ref003","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1038\/cr.2013.151","article-title":"Protein post-translational modifications and regulation of pluripotency in human stem cells","volume":"24","author":"YC Wang","year":"2014","journal-title":"Cell Res"},{"key":"pcbi.1010690.ref004","first-page":"1","article-title":"Proteomic Analysis of Posttranslational Modifications in Neurobiology. 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Wu","year":"2006","journal-title":"Mol Cell Proteomics"},{"issue":"9","key":"pcbi.1010690.ref032","doi-asserted-by":"crossref","first-page":"2131","DOI":"10.1074\/mcp.M900148-MCP200","article-title":"Epidermal growth factor receptor phosphorylation sites Ser991 and Tyr998 are implicated in the regulation of receptor endocytosis and phosphorylations at Ser1039 and Thr1041","volume":"8","author":"J Tong","year":"2009","journal-title":"Mol Cell Proteomics"},{"issue":"2","key":"pcbi.1010690.ref033","doi-asserted-by":"crossref","DOI":"10.1083\/jcb.201902073","article-title":"Phosphorylation of PKCdelta by FER tips the balance from EGFR degradation to recycling","volume":"220","author":"A Lonic","year":"2021","journal-title":"J Cell Biol"},{"issue":"2","key":"pcbi.1010690.ref034","doi-asserted-by":"crossref","first-page":"419","DOI":"10.1016\/j.celrep.2012.07.006","article-title":"Proteomic analysis of lysine acetylation sites in rat tissues reveals organ specificity and subcellular 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Jung","year":"2002","journal-title":"J Biol Chem"},{"issue":"21","key":"pcbi.1010690.ref038","doi-asserted-by":"crossref","first-page":"3971","DOI":"10.1091\/mbc.e11-02-0136","article-title":"Coupling of T161 and T14 phosphorylations protects cyclin B-CDK1 from premature activation","volume":"22","author":"K Coulonval","year":"2011","journal-title":"Mol Biol Cell"},{"issue":"Pt 5","key":"pcbi.1010690.ref039","first-page":"994","article-title":"The non-receptor tyrosine kinase Ack1 regulates the fate of activated EGFR by inducing trafficking to the p62\/NBR1 pre-autophagosome","volume":"127","author":"S Jones","year":"2014","journal-title":"J Cell Sci"},{"issue":"29","key":"pcbi.1010690.ref040","doi-asserted-by":"crossref","first-page":"48471","DOI":"10.18632\/oncotarget.17265","article-title":"Cell matrix adhesions in cancer: The proteins that form the glue","volume":"8","author":"M Maziveyi","year":"2017","journal-title":"Oncotarget"},{"issue":"12","key":"pcbi.1010690.ref041","doi-asserted-by":"crossref","first-page":"1271","DOI":"10.1038\/s41588-020-00736-4","article-title":"Reevaluating the roles of histone-modifying enzymes and their associated chromatin modifications in transcriptional regulation","volume":"52","author":"MAJ Morgan","year":"2020","journal-title":"Nat Genet"},{"issue":"4","key":"pcbi.1010690.ref042","doi-asserted-by":"crossref","first-page":"308","DOI":"10.1038\/nsmb740","article-title":"Regulation of the p300 HAT domain via a novel activation loop","volume":"11","author":"PR Thompson","year":"2004","journal-title":"Nat Struct Mol Biol"},{"key":"pcbi.1010690.ref043","doi-asserted-by":"crossref","first-page":"269","DOI":"10.1016\/0378-8733(83)90028-X","article-title":"Network structure and minimum degree","volume":"5","author":"SB Seidman","year":"1983","journal-title":"Social 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Amino Acid Transporter 1 Regulates Cancer Stemness and the Expression of Programmed Cell Death 1 Ligand 1 in Lung Cancer Cells.","volume":"22","author":"YH Liu","year":"2021","journal-title":"Int J Mol Sci"},{"issue":"2","key":"pcbi.1010690.ref055","doi-asserted-by":"crossref","first-page":"436","DOI":"10.1172\/JCI111718","article-title":"Functional compartmentation of glycolytic versus oxidative metabolism in isolated rabbit heart","volume":"75","author":"J Weiss","year":"1985","journal-title":"J Clin Invest"},{"issue":"20","key":"pcbi.1010690.ref056","doi-asserted-by":"crossref","first-page":"2269","DOI":"10.1091\/mbc.E20-02-0135","article-title":"PAG1 directs SRC-family kinase intracellular localization to mediate receptor tyrosine kinase-induced differentiation","volume":"31","author":"L Foltz","year":"2020","journal-title":"Mol Biol 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