Featured Publications
EGFR Ligands Differentially Stabilize Receptor Dimers to Specify Signaling Kinetics
Freed DM, Bessman NJ, Kiyatkin A, Salazar-Cavazos E, Byrne PO, Moore JO, Valley CC, Ferguson KM, Leahy DJ, Lidke DS, Lemmon MA. EGFR Ligands Differentially Stabilize Receptor Dimers to Specify Signaling Kinetics. Cell 2017, 171: 683-695.e18. PMID: 28988771, PMCID: PMC5650921, DOI: 10.1016/j.cell.2017.09.017.Peer-Reviewed Original ResearchConceptsReceptor tyrosine kinasesEpidermal growth factor receptorEGFR ligandsEGFR extracellular regionG protein-coupled receptorsDifferent EGFR ligandsCellular programsDifferent activating ligandsEGFR dimersCell signalingGrowth factor receptorExtracellular regionDimeric conformationEGFR dimerizationNew therapeutic opportunitiesReceptor dimersTyrosine kinaseBreast cancer cellsDimerization strengthActivating ligandsFactor receptorCancer cellsEpigenTherapeutic opportunitiesBiased agonism
2020
Comparison of tyrosine kinase domain properties for the neurotrophin receptors TrkA and TrkB.
Artim SC, Kiyatkin A, Lemmon MA. Comparison of tyrosine kinase domain properties for the neurotrophin receptors TrkA and TrkB. Biochemical Journal 2020, 477: 4053-4070. PMID: 33043964, PMCID: PMC7606831, DOI: 10.1042/bcj20200695.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBrain-Derived Neurotrophic FactorCatalytic DomainCell DifferentiationCell ProliferationGene Knockdown TechniquesKineticsMutationNerve Growth FactorsNerve Tissue ProteinsNeuroblastomaPC12 CellsPhosphorylationProtein DomainsRatsReceptor, trkAReceptor, trkBReceptors, Growth FactorRecombinant ProteinsRNA, Small InterferingSignal TransductionConceptsReceptor tyrosine kinasesLevels of p75NTRTropomyosin-related kinase (Trk) familyNeurotrophin receptors TrkAFunction of neurons
2017
Modeling of Receptor Tyrosine Kinase Signaling: Computational and Experimental Protocols
Fey D, Aksamitiene E, Kiyatkin A, Kholodenko BN. Modeling of Receptor Tyrosine Kinase Signaling: Computational and Experimental Protocols. Methods In Molecular Biology 2017, 1636: 417-453. PMID: 28730495, DOI: 10.1007/978-1-4939-7154-1_27.Peer-Reviewed Original ResearchConceptsReceptor tyrosine kinasesReceptor tyrosine kinase signalingMultiple cellular processesTyrosine kinase signalingCellular processesProtein phosphorylationKinase signalingNetwork biologySystems biologyTyrosine kinaseCell survivalIntegration of experimentsPowerful approachIntegrative approachBiologyComputational protocolQuantitative datasetsKinasePhosphorylationSignalingIdentification of salientApoptosisDifferentiationGlucose metabolismRegulation
2003
Tyr-317 Phosphorylation Increases Shc Structural Rigidity and Reduces Coupling of Domain Motions Remote from the Phosphorylation Site as Revealed by Molecular Dynamics Simulations*
Suenaga A, Kiyatkin AB, Hatakeyama M, Futatsugi N, Okimoto N, Hirano Y, Narumi T, Kawai A, Susukita R, Koishi T, Furusawa H, Yasuoka K, Takada N, Ohno Y, Taiji M, Ebisuzaki T, Hoek JB, Konagaya A, Kholodenko BN. Tyr-317 Phosphorylation Increases Shc Structural Rigidity and Reduces Coupling of Domain Motions Remote from the Phosphorylation Site as Revealed by Molecular Dynamics Simulations*. Journal Of Biological Chemistry 2003, 279: 4657-4662. PMID: 14613932, DOI: 10.1074/jbc.m310598200.Peer-Reviewed Original ResearchConceptsPhosphotyrosine bindingTyr-317Shc phosphorylationSH2 domainC-terminal Src homology 2 domainSrc homology 2 domainRas/Raf/MEK/ERK pathwayShc adaptor proteinRaf/MEK/ERK pathwayMEK/ERK pathwayReceptor tyrosine kinasesShc functionPhosphorylated ShcPhosphorylation sitesAdaptor proteinLinker regionShcTyrosine kinaseERK pathwayMembrane receptorsPhosphorylationDomain motionMolecular dynamics simulationsNumerous partnersDomain coupling