2018
Structural Basis for MARK1 Kinase Autoinhibition by Its KA1 Domain
Emptage RP, Lemmon MA, Ferguson KM, Marmorstein R. Structural Basis for MARK1 Kinase Autoinhibition by Its KA1 Domain. Structure 2018, 26: 1137-1143.e3. PMID: 30099988, PMCID: PMC6092042, DOI: 10.1016/j.str.2018.05.008.Peer-Reviewed Original ResearchMeSH KeywordsBinding SitesCheckpoint Kinase 1Cloning, MolecularCrystallography, X-RayEscherichia coliGene ExpressionGenetic VectorsHumansKineticsModels, MolecularMutationPeptidesProtein BindingProtein Conformation, alpha-HelicalProtein Conformation, beta-StrandProtein Interaction Domains and MotifsProtein Serine-Threonine KinasesRecombinant ProteinsStructural Homology, ProteinSubstrate SpecificityThermodynamicsConceptsKA1 domainSer/Thr protein kinaseKinase structureRelated kinasesUBA domainKinase domainProtein kinaseStructural basisC-terminusUnexpected interfaceC-lobeKinaseΑD helixPotential new avenuesAutoinhibitoryData implicateDomain surfaceDomainNew avenuesYeastAutoinhibitionCrystal structureHelixAlzheimer's diseaseVariants
2017
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 agonismMolecular determinants of KA1 domain-mediated autoinhibition and phospholipid activation of MARK1 kinase.
Emptage RP, Lemmon MA, Ferguson KM. Molecular determinants of KA1 domain-mediated autoinhibition and phospholipid activation of MARK1 kinase. Biochemical Journal 2017, 474: 385-398. PMID: 27879374, PMCID: PMC5317272, DOI: 10.1042/bcj20160792.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid MotifsBinding SitesCloning, MolecularEnzyme AssaysEscherichia coliGene ExpressionHumansKineticsMitogen-Activated Protein Kinase 1Models, MolecularPeptidesPhospholipidsProtein BindingProtein Interaction Domains and MotifsProtein Structure, SecondaryRecombinant ProteinsScattering, Small AngleSubstrate SpecificityX-Ray DiffractionConceptsKA1 domainMAP/microtubule affinity-regulating kinasesMicrotubule affinity-regulating kinaseGroup of kinasesIntramolecular autoinhibitory interactionAnionic phospholipid bindingAnionic phospholipidsSite-directed mutagenesisAutoinhibitory interactionsRegulatory modulesAutoinhibitory roleProtein modulesMembrane-bound targetsRelated kinasesBind membranesFamily kinasesKinase domainProtein kinasePhospholipid activationC-terminusRegulatory mechanismsPhospholipid bindingMechanistic basisKinaseAutoinhibitory activity