{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,31]],"date-time":"2025-12-31T11:21:36Z","timestamp":1767180096242,"version":"build-2238731810"},"update-to":[{"DOI":"10.1371\/journal.pcbi.1012488","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2024,10,11]],"date-time":"2024-10-11T00:00:00Z","timestamp":1728604800000}}],"reference-count":64,"publisher":"Public Library of Science (PLoS)","issue":"10","license":[{"start":{"date-parts":[[2024,10,1]],"date-time":"2024-10-01T00:00:00Z","timestamp":1727740800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100002347","name":"Bundesministerium f\u00fcr Bildung und Forschung","doi-asserted-by":"publisher","award":["031A428B"],"award-info":[{"award-number":["031A428B"]}],"id":[{"id":"10.13039\/501100002347","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002347","name":"Bundesministerium f\u00fcr Bildung und Forschung","doi-asserted-by":"publisher","award":["031A428G"],"award-info":[{"award-number":["031A428G"]}],"id":[{"id":"10.13039\/501100002347","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002347","name":"Federal Ministry of Education and Research","doi-asserted-by":"crossref","award":["MSTARS-2 (16LW0239K, 16LW0240)"],"award-info":[{"award-number":["MSTARS-2 (16LW0239K, 16LW0240)"]}],"id":[{"id":"10.13039\/501100002347","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100005972","name":"Deutsche Krebshilfe","doi-asserted-by":"publisher","award":["70114307"],"award-info":[{"award-number":["70114307"]}],"id":[{"id":"10.13039\/501100005972","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100008658","name":"Deutsches Krebsforschungszentrum","doi-asserted-by":"publisher","award":["Young Investigator Grant"],"award-info":[{"award-number":["Young Investigator Grant"]}],"id":[{"id":"10.13039\/100008658","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100008751","name":"Bundesinstitut f\u00fcr Risikobewertung","doi-asserted-by":"publisher","award":["60-0102-01.P61"],"award-info":[{"award-number":["60-0102-01.P61"]}],"id":[{"id":"10.13039\/501100008751","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.ploscompbiol.org"],"crossmark-restriction":false},"short-container-title":["PLoS Comput Biol"],"abstract":"<jats:p>B cell receptor (BCR) signaling is required for the survival and maturation of B cells and is deregulated in B cell lymphomas. While proximal BCR signaling is well studied, little is known about the crosstalk of downstream effector pathways, and a comprehensive quantitative network analysis of BCR signaling is missing. Here, we semi-quantitatively modelled BCR signaling in Burkitt lymphoma (BL) cells using systematically perturbed phosphorylation data of BL-2 and BL-41 cells. The models unveiled feedback and crosstalk structures in the BCR signaling network, including a negative crosstalk from p38 to MEK\/ERK. The relevance of the crosstalk was verified for BCR and CD40 signaling in different BL cells and confirmed by global phosphoproteomics on ERK itself and known ERK target sites. Compared to the starting network, the trained network for BL-2 cells was better transferable to BL-41 cells. Moreover, the BL-2 network was also suited to model BCR signaling in Diffuse large B cell lymphoma cells lines with aberrant BCR signaling (HBL-1, OCI-LY3), indicating that BCR aberration does not cause a major downstream rewiring.<\/jats:p>","DOI":"10.1371\/journal.pcbi.1012488","type":"journal-article","created":{"date-parts":[[2024,10,1]],"date-time":"2024-10-01T13:30:19Z","timestamp":1727789419000},"page":"e1012488","update-policy":"https:\/\/doi.org\/10.1371\/journal.pcbi.corrections_policy","source":"Crossref","is-referenced-by-count":0,"title":["Quantitative modeling of signaling in aggressive B cell lymphoma unveils conserved core network"],"prefix":"10.1371","volume":"20","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0242-1506","authenticated-orcid":true,"given":"Bertram","family":"Klinger","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Isabel","family":"Rausch","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6588-8547","authenticated-orcid":true,"given":"Anja","family":"Sieber","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Helmut","family":"Kutz","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vanessa","family":"Kruse","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7049-534X","authenticated-orcid":true,"given":"Marieluise","family":"Kirchner","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2245-528X","authenticated-orcid":true,"given":"Philipp","family":"Mertins","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0783-1950","authenticated-orcid":true,"given":"Arnd","family":"Kieser","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0171-7447","authenticated-orcid":true,"given":"Nils","family":"Bl\u00fcthgen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7760-525X","authenticated-orcid":true,"given":"Dieter","family":"Kube","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"340","published-online":{"date-parts":[[2024,10,1]]},"reference":[{"issue":"1","key":"pcbi.1012488.ref001","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1186\/s12943-018-0779-z","article-title":"Role of Bruton\u2019s tyrosine kinase in B cells and malignancies","volume":"17","author":"S Pal Singh","year":"2018","journal-title":"Molecular Cancer"},{"issue":"6","key":"pcbi.1012488.ref002","doi-asserted-by":"crossref","first-page":"a018788","DOI":"10.1101\/cshperspect.a018788","article-title":"Signaling in Lymphocyte Activation","volume":"7","author":"D. Cantrell","year":"2015","journal-title":"Cold Spring Harb Perspect Biol"},{"issue":"5","key":"pcbi.1012488.ref003","doi-asserted-by":"crossref","first-page":"701","DOI":"10.1016\/j.immuni.2006.10.010","article-title":"Antigen-Receptor Signaling to Nuclear Factor \u03baB","volume":"25","author":"J Schulze-Luehrmann","year":"2006","journal-title":"Immunity"},{"issue":"5600","key":"pcbi.1012488.ref004","doi-asserted-by":"crossref","first-page":"1911","DOI":"10.1126\/science.1072682","article-title":"Mitogen-activated protein kinase pathways mediated by ERK, JNK, and p38 protein kinases","volume":"298","author":"GL Johnson","year":"2002","journal-title":"Science"},{"issue":"1","key":"pcbi.1012488.ref005","doi-asserted-by":"crossref","first-page":"4244","DOI":"10.1038\/s41598-018-22544-x","article-title":"Grb2 and GRAP connect the B cell antigen receptor to Erk MAP kinase activation in human B cells","volume":"8","author":"K Vanshylla","year":"2018","journal-title":"Scientific Reports"},{"issue":"6","key":"pcbi.1012488.ref006","doi-asserted-by":"crossref","first-page":"810","DOI":"10.15252\/msb.20145880","article-title":"Systems-wide analysis of BCR signalosomes and downstream phosphorylation and ubiquitylation","volume":"11","author":"S Satpathy","year":"2015","journal-title":"Mol Syst Biol"},{"issue":"8","key":"pcbi.1012488.ref007","doi-asserted-by":"crossref","first-page":"995","DOI":"10.1182\/blood-2016-10-747303","article-title":"Tonic B-cell receptor signaling in diffuse large B-cell lymphoma","volume":"130","author":"O Havranek","year":"2017","journal-title":"Blood"},{"issue":"7418","key":"pcbi.1012488.ref008","doi-asserted-by":"crossref","first-page":"116","DOI":"10.1038\/nature11378","article-title":"Burkitt lymphoma pathogenesis and therapeutic targets from structural and functional genomics","volume":"490","author":"R Schmitz","year":"2012","journal-title":"Nature"},{"issue":"7277","key":"pcbi.1012488.ref009","doi-asserted-by":"crossref","first-page":"88","DOI":"10.1038\/nature08638","article-title":"Chronic active B-cell-receptor signalling in diffuse large B-cell lymphoma","volume":"463","author":"RE Davis","year":"2010","journal-title":"Nature"},{"issue":"1","key":"pcbi.1012488.ref010","doi-asserted-by":"crossref","first-page":"198","DOI":"10.1111\/imr.12738","article-title":"The B-cell receptor in control of tumor B-cell fitness: Biology and clinical relevance","volume":"288","author":"S Casola","year":"2019","journal-title":"Immunol Rev"},{"issue":"4","key":"pcbi.1012488.ref011","doi-asserted-by":"crossref","first-page":"269","DOI":"10.1038\/nri1335","article-title":"Feedback regulation of lymphocyte signalling","volume":"4","author":"M Reth","year":"2004","journal-title":"Nature Reviews Immunology"},{"issue":"6","key":"pcbi.1012488.ref012","doi-asserted-by":"crossref","first-page":"1396","DOI":"10.3390\/cancers12061396","article-title":"Mechanisms of B Cell Receptor Activation and Responses to B Cell Receptor Inhibitors in B Cell Malignancies","volume":"12","author":"DG Efremov","year":"2020","journal-title":"Cancers"},{"issue":"15","key":"pcbi.1012488.ref013","doi-asserted-by":"crossref","first-page":"1417","DOI":"10.1056\/NEJMra0807082","article-title":"Aggressive Lymphomas.","volume":"362","author":"G Lenz","year":"2010","journal-title":"New England Journal of Medicine"},{"key":"pcbi.1012488.ref014","doi-asserted-by":"crossref","first-page":"565","DOI":"10.1146\/annurev-immunol-020711-075027","volume":"30","author":"AL Shaffer","year":"2012","journal-title":"Annu Rev Immunol"},{"issue":"21","key":"pcbi.1012488.ref015","doi-asserted-by":"crossref","first-page":"2307","DOI":"10.1182\/blood-2017-11-764332","article-title":"Genetics of diffuse large B-cell lymphoma","volume":"131","author":"L Pasqualucci","year":"2018","journal-title":"Blood"},{"issue":"3","key":"pcbi.1012488.ref016","doi-asserted-by":"crossref","first-page":"401","DOI":"10.1016\/j.bbamcr.2015.07.009","article-title":"Microenvironment interactions and B-cell receptor signaling in Chronic Lymphocytic Leukemia: Implications for disease pathogenesis and treatment","volume":"1863","author":"E ten Hacken","year":"2016","journal-title":"Biochimica et Biophysica Acta (BBA)\u2014Molecular Cell Research"},{"issue":"2","key":"pcbi.1012488.ref017","doi-asserted-by":"crossref","first-page":"a014282","DOI":"10.1101\/cshperspect.a014282","article-title":"Oncogenic Mechanisms in Burkitt Lymphoma","volume":"4","author":"R Schmitz","year":"2014","journal-title":"Cold Spring Harb. Perspect. Med"},{"key":"pcbi.1012488.ref018","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1146\/annurev-pathol-020117-043803","article-title":"New Insights into Lymphoma Pathogenesis","volume":"13","author":"KSJ Elenitoba-Johnson","year":"2018","journal-title":"Annu Rev Pathol"},{"issue":"7718","key":"pcbi.1012488.ref019","doi-asserted-by":"crossref","first-page":"387","DOI":"10.1038\/s41586-018-0290-0","article-title":"A multiprotein supercomplex controlling oncogenic signalling in lymphoma","volume":"560","author":"JD Phelan","year":"2018","journal-title":"Nature"},{"issue":"1","key":"pcbi.1012488.ref020","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1186\/1478-811X-10-43","article-title":"Global gene expression changes of in vitro stimulated human transformed germinal centre B cells as surrogate for oncogenic pathway activation in individual aggressive B cell lymphomas","volume":"10","author":"A Schrader","year":"2012","journal-title":"Cell Communication and Signaling"},{"issue":"11","key":"pcbi.1012488.ref021","doi-asserted-by":"crossref","first-page":"e97980","DOI":"10.15252\/embj.201797980","article-title":"Continuous signaling of CD79b and CD19 is required for the fitness of Burkitt lymphoma B cells","volume":"37","author":"X He","year":"2018","journal-title":"EMBO J"},{"issue":"8","key":"pcbi.1012488.ref022","doi-asserted-by":"crossref","first-page":"1580","DOI":"10.1371\/journal.pcbi.0030163","article-title":"A logical model provides insights into T cell receptor signaling","volume":"3","author":"J Saez-Rodriguez","year":"2007","journal-title":"PLoS Comput Biol"},{"issue":"2","key":"pcbi.1012488.ref023","doi-asserted-by":"crossref","first-page":"1296","DOI":"10.1074\/jbc.M109.055863","article-title":"Integration of a Phosphatase Cascade with the Mitogen-activated Protein Kinase Pathway Provides for a Novel Signal Processing Function","volume":"285","author":"VK Chaudhri","year":"2010","journal-title":"J Biol Chem"},{"key":"pcbi.1012488.ref024","doi-asserted-by":"crossref","first-page":"150","DOI":"10.1038\/msb4100197","article-title":"Capturing cell-fate decisions from the molecular signatures of a receptor-dependent signaling response","volume":"3","author":"D Kumar","year":"2007","journal-title":"Mol Syst Biol"},{"issue":"1","key":"pcbi.1012488.ref025","doi-asserted-by":"crossref","first-page":"429","DOI":"10.1146\/annurev-cancerbio-030518-055734","article-title":"Taming the Heterogeneity of Aggressive Lymphomas for Precision Therapy","volume":"3","author":"RM Young","year":"2019","journal-title":"Annu Rev Cancer Biol"},{"issue":"1","key":"pcbi.1012488.ref026","doi-asserted-by":"crossref","first-page":"673","DOI":"10.1038\/msb.2013.29","article-title":"Network quantification of EGFR signaling unveils potential for targeted combination therapy","volume":"9","author":"B Klinger","year":"2013","journal-title":"Mol Syst Biol"},{"issue":"6","key":"pcbi.1012488.ref027","doi-asserted-by":"crossref","first-page":"1583","DOI":"10.1046\/j.1432-1327.2000.01197.x","article-title":"Negative feedback and ultrasensitivity can bring about oscillations in the mitogen-activated protein kinase cascades","volume":"267","author":"BN Kholodenko","year":"2000","journal-title":"European journal of biochemistry \/ FEBS"},{"issue":"4","key":"pcbi.1012488.ref028","doi-asserted-by":"crossref","first-page":"370","DOI":"10.1038\/nbt0402-370","article-title":"Computational modeling of the dynamics of the MAP kinase cascade activated by surface and internalized EGF receptors","volume":"20","author":"B Schoeberl","year":"2002","journal-title":"Nat Biotechnol"},{"issue":"2","key":"pcbi.1012488.ref029","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1038\/s41419-020-2308-4","article-title":"SIRT1 inhibits chemoresistance and cancer stemness of gastric cancer by initiating an AMPK\/FOXO3 positive feedback loop","volume":"11","author":"Y An","year":"2020","journal-title":"Cell Death & Disease"},{"issue":"1","key":"pcbi.1012488.ref030","doi-asserted-by":"crossref","first-page":"86","DOI":"10.1016\/j.celrep.2014.02.045","article-title":"Intrinsic resistance to MEK inhibition in KRAS mutant lung and colon cancer through transcriptional induction of ERBB3","volume":"7","author":"C Sun","year":"2014","journal-title":"Cell Rep"},{"key":"pcbi.1012488.ref031","doi-asserted-by":"crossref","first-page":"800140","DOI":"10.3389\/fonc.2022.800140","article-title":"The Role of Feedback Loops in Targeted Therapy for Pancreatic Cancer","volume":"12","author":"W Gu","year":"2022","journal-title":"Front Oncol"},{"issue":"8","key":"pcbi.1012488.ref032","doi-asserted-by":"crossref","first-page":"506","DOI":"10.1038\/s41571-021-00495-z","article-title":"Precision oncology in metastatic colorectal cancer\u2014from biology to medicine","volume":"18","author":"F Di Nicolantonio","year":"2021","journal-title":"Nature Reviews Clinical Oncology"},{"issue":"7387","key":"pcbi.1012488.ref033","doi-asserted-by":"crossref","first-page":"100","DOI":"10.1038\/nature10868","article-title":"Unresponsiveness of colon cancer to BRAF(V600E) inhibition through feedback activation of EGFR","volume":"483","author":"A Prahallad","year":"2012","journal-title":"Nature"},{"issue":"2","key":"pcbi.1012488.ref034","doi-asserted-by":"crossref","first-page":"646","DOI":"10.4049\/jimmunol.1102003","article-title":"A computational model for early events in B cell antigen receptor signaling: analysis of the roles of Lyn and Fyn","volume":"189","author":"D Barua","year":"2012","journal-title":"J Immunol"},{"key":"pcbi.1012488.ref035","doi-asserted-by":"crossref","first-page":"75","DOI":"10.3390\/pr3010075","article-title":"A Computational Study of the Effects of Syk Activity on B Cell Receptor Signaling Dynamics","volume":"3","author":"RL Mcgee","year":"2015","journal-title":"Processes (Basel)"},{"issue":"6","key":"pcbi.1012488.ref036","doi-asserted-by":"crossref","first-page":"893","DOI":"10.1093\/bioinformatics\/btv680","article-title":"Analyzing synergistic and non-synergistic interactions in signalling pathways using Boolean Nested Effect Models","volume":"32","author":"M Pirkl","year":"2016","journal-title":"Bioinformatics"},{"issue":"12","key":"pcbi.1012488.ref037","doi-asserted-by":"crossref","first-page":"3364","DOI":"10.1158\/0008-5472.CAN-17-0078","article-title":"Drug resistance mechanisms in colorectal cancer dissected with cell type-specific dynamic logic models","volume":"77","author":"F Eduati","year":"2017","journal-title":"Cancer Res"},{"issue":"20","key":"pcbi.1012488.ref038","doi-asserted-by":"crossref","first-page":"12841","DOI":"10.1073\/pnas.192442699","article-title":"Untangling the wires: a strategy to trace functional interactions in signaling and gene networks","volume":"99","author":"BN Kholodenko","year":"2002","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"23","key":"pcbi.1012488.ref039","doi-asserted-by":"crossref","first-page":"4079","DOI":"10.1093\/bioinformatics\/bty473","article-title":"Modelling signalling networks from perturbation data","volume":"34","author":"M Dorel","year":"2018","journal-title":"Bioinformatics"},{"issue":"9","key":"pcbi.1012488.ref040","doi-asserted-by":"crossref","first-page":"1108","DOI":"10.1091\/mbc.E18-10-0676","article-title":"Isoform-specific Ras signaling is growth factor dependent. Chernoff J, editor","volume":"30","author":"FE Hood","year":"2019","journal-title":"Mol Biol Cell"},{"issue":"11","key":"pcbi.1012488.ref041","doi-asserted-by":"crossref","first-page":"e1009515","DOI":"10.1371\/journal.pcbi.1009515","article-title":"Neuroblastoma signalling models unveil combination therapies targeting feedback-mediated resistance","volume":"17","author":"M Dorel","year":"2021","journal-title":"PLoS Comput Biol"},{"issue":"1","key":"pcbi.1012488.ref042","doi-asserted-by":"crossref","first-page":"126","DOI":"10.1186\/s12943-022-01583-z","article-title":"Mutations in ALK signaling pathways conferring resistance to ALK inhibitor treatment lead to collateral vulnerabilities in neuroblastoma cells","volume":"21","author":"M Berlak","year":"2022","journal-title":"Molecular Cancer"},{"issue":"11","key":"pcbi.1012488.ref043","doi-asserted-by":"crossref","first-page":"e11510","DOI":"10.15252\/msb.202211510","article-title":"Modeling unveils sex differences of signaling networks in mouse embryonic stem cells","volume":"19","author":"Z Sultana","year":"2023","journal-title":"Mol Syst Biol"},{"issue":"3","key":"pcbi.1012488.ref044","doi-asserted-by":"crossref","first-page":"1306","DOI":"10.4049\/jimmunol.164.3.1306","article-title":"T cells can induce somatic mutation in B cell receptor-engaged BL2 Burkitt\u2019s lymphoma cells independently of CD40-CD40 ligand interactions","volume":"164","author":"S Den\u00e9poux","year":"2000","journal-title":"J Immunol"},{"issue":"14","key":"pcbi.1012488.ref045","doi-asserted-by":"crossref","first-page":"7976","DOI":"10.1073\/pnas.141222198","article-title":"Expression of error-prone polymerases in BL2 cells activated for Ig somatic hypermutation","volume":"98","author":"V Poltoratsky","year":"2001","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"4","key":"pcbi.1012488.ref046","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1038\/nrc3702","article-title":"Targeting Bruton\u2019s tyrosine kinase in B cell malignancies","volume":"14","author":"RW Hendriks","year":"2014","journal-title":"Nat Rev Cancer"},{"issue":"15","key":"pcbi.1012488.ref047","doi-asserted-by":"crossref","first-page":"1923","DOI":"10.1093\/bioinformatics\/btp358","article-title":"Structural and practical identifiability analysis of partially observed dynamical models by exploiting the profile likelihood","volume":"25","author":"A Raue","year":"2009","journal-title":"Bioinformatics"},{"issue":"4","key":"pcbi.1012488.ref048","doi-asserted-by":"crossref","first-page":"101801","DOI":"10.1016\/j.jbc.2022.101801","article-title":"Phosphoproteomic analysis of thrombin- and p38 MAPK-regulated signaling networks in endothelial cells","volume":"298","author":"O Molinar-Inglis","year":"2022","journal-title":"Journal of Biological Chemistry"},{"issue":"5","key":"pcbi.1012488.ref049","doi-asserted-by":"crossref","first-page":"1002","DOI":"10.1016\/j.cellsig.2011.12.021","article-title":"Dual specificity phosphatases 10 and 16 are positive regulators of EGF-stimulated ERK activity: Indirect regulation of ERK signals by JNK\/p38 selective MAPK phosphatases","volume":"24","author":"AR Finch","year":"2012","journal-title":"Cell Signal"},{"key":"pcbi.1012488.ref050","doi-asserted-by":"crossref","DOI":"10.3389\/fphys.2012.00475","article-title":"How scaffolds shape MAPK signaling: What we know and opportunities for systems approaches","volume":"3","author":"F Witzel","year":"2012","journal-title":"Front Physiol"},{"issue":"2","key":"pcbi.1012488.ref051","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1016\/j.molcel.2004.11.055","article-title":"Regulation of Raf-1 by Direct Feedback Phosphorylation","volume":"17","author":"MK Dougherty","year":"2005","journal-title":"Mol Cell"},{"issue":"8","key":"pcbi.1012488.ref052","doi-asserted-by":"crossref","first-page":"4509","DOI":"10.1128\/MCB.17.8.4509","article-title":"Phosphorylation of Raf-1 Serine 338-Serine 339 Is an Essential Regulatory Event for Ras-Dependent Activation and Biological Signaling","volume":"17","author":"B Diaz","year":"1997","journal-title":"Mol Cell Biol"},{"issue":"7","key":"pcbi.1012488.ref053","doi-asserted-by":"crossref","first-page":"1632","DOI":"10.1038\/s41596-018-0006-9","article-title":"Reproducible workflow for multiplexed deep-scale proteome and phosphoproteome analysis of tumor tissues by liquid chromatography-mass spectrometry","volume":"13","author":"P Mertins","year":"2018","journal-title":"Nat Protoc"},{"key":"pcbi.1012488.ref054","doi-asserted-by":"crossref","first-page":"D512","DOI":"10.1093\/nar\/gku1267","article-title":"PhosphoSitePlus, 2014: mutations, PTMs and recalibrations","volume":"43","author":"P V. Hornbeck","year":"2015","journal-title":"Nucleic Acids Res"},{"issue":"17","key":"pcbi.1012488.ref055","doi-asserted-by":"crossref","first-page":"2607","DOI":"10.1002\/1873-3468.12740","article-title":"A Compendium of ERK Targets","volume":"591","author":"EB \u00dcnal","year":"2017","journal-title":"FEBS Lett"},{"issue":"12","key":"pcbi.1012488.ref056","doi-asserted-by":"crossref","first-page":"2796","DOI":"10.1074\/mcp.M900285-MCP200","article-title":"Global Effects of Kinase Inhibitors on Signaling Networks Revealed by Quantitative Phosphoproteomics","volume":"8","author":"C Pan","year":"2009","journal-title":"Mol Cell Proteomics"},{"issue":"10","key":"pcbi.1012488.ref057","doi-asserted-by":"crossref","first-page":"113017","DOI":"10.1016\/j.celrep.2023.113017","article-title":"Negative feedback regulation of MAPK signaling is an important driver of chronic lymphocytic leukemia progression","volume":"42","author":"V Ecker","year":"2023","journal-title":"Cell Rep"},{"issue":"5","key":"pcbi.1012488.ref058","doi-asserted-by":"crossref","first-page":"281","DOI":"10.1038\/nrm3979","article-title":"Regulation of RAF protein kinases in ERK signalling","volume":"16","author":"H Lavoie","year":"2015","journal-title":"Nat Rev Mol Cell Biol"},{"issue":"10","key":"pcbi.1012488.ref059","doi-asserted-by":"crossref","first-page":"6905","DOI":"10.1074\/jbc.C000917200","article-title":"Stress-induced Inhibition of ERK1 and ERK2 by Direct Interaction with p38 MAP Kinase","volume":"276","author":"H Zhang","year":"2001","journal-title":"Journal of Biological Chemistry"},{"key":"pcbi.1012488.ref060","doi-asserted-by":"crossref","first-page":"489","DOI":"10.1038\/msb.2011.27","article-title":"Strong negative feedback from Erk to Raf confers robustness to MAPK signalling","volume":"7","author":"R Fritsche-Guenther","year":"2011","journal-title":"Mol Syst Biol"},{"issue":"5","key":"pcbi.1012488.ref061","doi-asserted-by":"crossref","first-page":"783","DOI":"10.1002\/ijc.34112","article-title":"Modeling the B-cell receptor signaling on single cell level reveals a stable network circuit topology between nonmalignant B cells and chronic lymphocytic leukemia cells and between untreated cells and cells treated with kinase inhibitors","volume":"151","author":"C Wolf","year":"2022","journal-title":"Int J Cancer"},{"issue":"4","key":"pcbi.1012488.ref062","doi-asserted-by":"crossref","first-page":"598","DOI":"10.1002\/ijc.20759","article-title":"The Epstein-Barr virus oncoprotein latent membrane protein 1 induces expression of the chemokine IP-10: Importance of mRNA half-life regulation","volume":"114","author":"M Vockerodt","year":"2005","journal-title":"Int J Cancer"},{"issue":"4","key":"pcbi.1012488.ref063","doi-asserted-by":"crossref","first-page":"507","DOI":"10.1016\/S0022-5193(02)93096-1","article-title":"Modular response analysis of cellular regulatory networks","volume":"218","author":"FJ Bruggeman","year":"2002","journal-title":"J Theor Biol"},{"issue":"5","key":"pcbi.1012488.ref064","doi-asserted-by":"crossref","first-page":"e0197162","DOI":"10.1371\/journal.pone.0197162","article-title":"A comparative study of RNA-Seq and microarray data analysis on the two examples of rectal-cancer patients and Burkitt Lymphoma cells","volume":"13","author":"A Wolff","year":"2018","journal-title":"PLoS One"}],"updated-by":[{"DOI":"10.1371\/journal.pcbi.1012488","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2024,10,11]],"date-time":"2024-10-11T00:00:00Z","timestamp":1728604800000}}],"container-title":["PLOS Computational Biology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pcbi.1012488","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,10,11]],"date-time":"2024-10-11T13:35:28Z","timestamp":1728653728000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pcbi.1012488"}},"subtitle":[],"editor":[{"given":"Marc R.","family":"Birtwistle","sequence":"first","affiliation":[],"role":[{"role":"editor","vocabulary":"crossref"}]}],"short-title":[],"issued":{"date-parts":[[2024,10,1]]},"references-count":64,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2024,10,1]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pcbi.1012488","relation":{},"ISSN":["1553-7358"],"issn-type":[{"value":"1553-7358","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,10,1]]}}}