2024
Systems modeling of oncogenic G-protein and GPCR signaling reveals unexpected differences in downstream pathway activation
Trogdon M, Abbott K, Arang N, Lande K, Kaur N, Tong M, Bakhoum M, Gutkind J, Stites E. Systems modeling of oncogenic G-protein and GPCR signaling reveals unexpected differences in downstream pathway activation. Npj Systems Biology And Applications 2024, 10: 75. PMID: 39013872, PMCID: PMC11252164, DOI: 10.1038/s41540-024-00400-1.Peer-Reviewed Original ResearchConceptsSignaling networksMathematical models of biochemical reaction networksModels of biochemical reaction networksG-proteinCell signaling networksDisease-causing mutationsComputational systems biologyBiochemical reaction networksDownstream pathway activationSignaling phenotypeSystems biologyBioinformatics analysisGPCR signalingMutationsCo-occurring mutationsOncogenic mutationsPathway activationDiscovery toolPathwayReaction networkSignalCYSLTR2 mutationsDiscoveryPhenotypeMutually-exclusive
2015
Use of Mechanistic Models to Integrate and Analyze Multiple Proteomic Datasets
Stites E, Aziz M, Creamer M, Von Hoff D, Posner R, Hlavacek W. Use of Mechanistic Models to Integrate and Analyze Multiple Proteomic Datasets. Biophysical Journal 2015, 108: 1819-1829. PMID: 25863072, PMCID: PMC4390817, DOI: 10.1016/j.bpj.2015.02.030.Peer-Reviewed Original ResearchConceptsEpidermal growth factor receptorExperimentally detected interactionsPhosphotyrosine-binding domainSrc homology 2Recruitment of proteinsCell line-specific modelsProtein copy numbersProtein-protein interactionsCell signaling networksEpidermal growth factor receptor signalingCell linesWell-characterized roleCell line-specific differencesLow-affinity interactionsLine-specific differencesActivation of EGFR signalingMultiple cell linesLigand-stimulated activationAutophosphorylation sitesSignaling networksProteomic datasetsCopy numberHomolog 2EGFR signalingMap interactions
2012
Specification, annotation, visualization and simulation of a large rule-based model for ERBB receptor signaling
Creamer M, Stites E, Aziz M, Cahill J, Tan C, Berens M, Han H, Bussey K, Von Hoff D, Hlavacek W, Posner R. Specification, annotation, visualization and simulation of a large rule-based model for ERBB receptor signaling. BMC Systems Biology 2012, 6: 107. PMID: 22913808, PMCID: PMC3485121, DOI: 10.1186/1752-0509-6-107.Peer-Reviewed Original ResearchConceptsCell signaling networksSignaling networksErbB receptor signalingRule-based modeling approachSignaling proteinsPost-translational modification stateSites of post-translational modificationsNetwork-free simulationCellular signaling networksProtein-protein interactionsPost-translational modificationsReceptor signalingSite of modificationActivation of ERKModification statesProtein complexesProtein interactionsContact mapsCellular signalingTyrosine residuesIndividual serinesDevelopment of softwareProteinRule-based modelKinetics of molecular interactions
2011
Mechanistic modeling to investigate signaling by oncogenic Ras mutants
Stites E, Ravichandran K. Mechanistic modeling to investigate signaling by oncogenic Ras mutants. WIREs Mechanisms Of Disease 2011, 4: 117-127. PMID: 21766467, DOI: 10.1002/wsbm.156.Peer-Reviewed Original ResearchConceptsCell signaling networksSignaling networksCancer phenotypeMutant Ras signalingAcquisition of mutationsRas signalingCell signalingBiochemistry of proteinsLevel of signalMutated genesExpression levelsBiochemical reaction mechanismsPhenotypeMechanistic modelInvestigated signalSignalGenesMutationsRasProteinCancerIndividual reactionsExpression