2020
Structural Insights into Pseudokinase Domains of Receptor Tyrosine Kinases
Sheetz JB, Mathea S, Karvonen H, Malhotra K, Chatterjee D, Niininen W, Perttilä R, Preuss F, Suresh K, Stayrook SE, Tsutsui Y, Radhakrishnan R, Ungureanu D, Knapp S, Lemmon MA. Structural Insights into Pseudokinase Domains of Receptor Tyrosine Kinases. Molecular Cell 2020, 79: 390-405.e7. PMID: 32619402, PMCID: PMC7543951, DOI: 10.1016/j.molcel.2020.06.018.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid SequenceAnimalsBaculoviridaeBinding SitesCell Adhesion MoleculesCell LineCloning, MolecularCrystallography, X-RayGene ExpressionHumansMiceModels, MolecularPrecursor Cells, B-LymphoidProtein BindingProtein Conformation, alpha-HelicalProtein Conformation, beta-StrandProtein Interaction Domains and MotifsProtein Kinase InhibitorsReceptor Protein-Tyrosine KinasesReceptor Tyrosine Kinase-like Orphan ReceptorsReceptors, Eph FamilyRecombinant ProteinsSf9 CellsSmall Molecule LibrariesSpodopteraStructural Homology, ProteinSubstrate SpecificityConceptsInsulin receptor kinasePseudokinase domainReceptor tyrosine kinasesTyrosine kinaseNon-catalytic functionsATP-binding pocketType II inhibitorsDomain plasticityActivation loopReceptor kinaseInactive conformationStructural insightsPseudokinasesATP siteStructural comparisonAromatic residuesKinaseAlternative interactionsApparent lackImportant roleDomainWntMotifROR1Residues
2015
Comparison of Saccharomyces cerevisiae F-BAR Domain Structures Reveals a Conserved Inositol Phosphate Binding Site
Moravcevic K, Alvarado D, Schmitz KR, Kenniston JA, Mendrola JM, Ferguson KM, Lemmon MA. Comparison of Saccharomyces cerevisiae F-BAR Domain Structures Reveals a Conserved Inositol Phosphate Binding Site. Structure 2015, 23: 352-363. PMID: 25620000, PMCID: PMC4319572, DOI: 10.1016/j.str.2014.12.009.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid SequenceBinding SitesCrystallography, X-RayGreen Fluorescent ProteinsGTPase-Activating ProteinsHeLa CellsHumansInositol PhosphatesModels, MolecularMolecular Sequence DataProtein Structure, TertiarySaccharomyces cerevisiaeSaccharomyces cerevisiae ProteinsSequence AlignmentSpecies SpecificityConceptsF-BAR domainLipid-binding specificityMembrane-binding propertiesNumerous functional studiesPhosphate binding siteUnappreciated determinantF-BARDomain bindsCell signalingCurved membranesMembrane interactionsFunctional studiesRgd1pBinding sitesX-ray crystal structureInositol phosphatesDomain structureDomainHof1pPhospholipidsRhoGAPCytokinesisEndocytosisPhosphoinositideSignaling
2013
Receptor tyrosine kinases with intracellular pseudokinase domains
Mendrola JM, Shi F, Park JH, Lemmon MA. Receptor tyrosine kinases with intracellular pseudokinase domains. Biochemical Society Transactions 2013, 41: 1029-1036. PMID: 23863174, PMCID: PMC3777422, DOI: 10.1042/bst20130104.Peer-Reviewed Original ResearchConceptsWeak kinase activityKinase activitySignificant kinase activityReceptor tyrosine kinasesPseudokinase domainHuman proteomeProtein kinaseImportant residuesWnt receptorsTyrosine kinaseEGFR familyKinaseFunctional studiesRTKPseudokinasesPseudokinaseProteomeReceptorsWntNew lightErbB3MutationsResiduesActivityRecent work
2012
Assessing the range of kinase autoinhibition mechanisms in the insulin receptor family
Artim SC, Mendrola JM, Lemmon MA. Assessing the range of kinase autoinhibition mechanisms in the insulin receptor family. Biochemical Journal 2012, 448: 213-220. PMID: 22992069, PMCID: PMC3492919, DOI: 10.1042/bj20121365.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid MotifsAmino Acid SequenceAntigens, CDCatalytic DomainCrystallography, X-RayEnzyme ActivationHumansIn Vitro TechniquesModels, MolecularMutationNeoplasmsProtein Structure, QuaternaryReceptor Tyrosine Kinase-like Orphan ReceptorsReceptor, InsulinReceptor, trkARecombinant Proteins
2010
Kinase Associated-1 Domains Drive MARK/PAR1 Kinases to Membrane Targets by Binding Acidic Phospholipids
Moravcevic K, Mendrola JM, Schmitz KR, Wang YH, Slochower D, Janmey PA, Lemmon MA. Kinase Associated-1 Domains Drive MARK/PAR1 Kinases to Membrane Targets by Binding Acidic Phospholipids. Cell 2010, 143: 966-977. PMID: 21145462, PMCID: PMC3031122, DOI: 10.1016/j.cell.2010.11.028.Peer-Reviewed Original ResearchConceptsKA1 domainBud neck localizationMembrane association domainAcidic phospholipidsImportance of phosphatidylserineAssociation domainMembrane associationMembrane localizationProtein kinaseC2 domainC-terminusMembrane targetsKinaseIntact proteinAnionic phospholipidsX-ray crystallographyNeck localizationPhosphatidylserinePhospholipidsCrucial roleDomainMembrane surfaceLocalizationTerminusRegulator
2008
Functional selectivity of EGF family peptide growth factors: Implications for cancer
Wilson KJ, Gilmore JL, Foley J, Lemmon MA, Riese DJ. Functional selectivity of EGF family peptide growth factors: Implications for cancer. Pharmacology & Therapeutics 2008, 122: 1-8. PMID: 19135477, PMCID: PMC2665203, DOI: 10.1016/j.pharmthera.2008.11.008.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid SequenceAnimalsAntineoplastic AgentsDrug Delivery SystemsEpidermal Growth FactorErbB ReceptorsHumansLigandsNeoplasmsSignal TransductionConceptsEGF family membersPeptide growth factorsFunctional selectivityGrowth factorErbB family receptorsFamily membersNeck cancerReceptor couplingReceptor tyrosine phosphorylationMalignant phenotypeDivergent biological responsesSame receptorFamily receptorsEGF familyReceptorsErbB receptorsG proteinsCancerCancer chemotherapeuticsCell culturesLigand activityTyrosine phosphorylationColorectalSubsequent differencesBiological responses
2006
The Dbs PH domain contributes independently to membrane targeting and regulation of guanine nucleotide-exchange activity
Baumeister MA, Rossman KL, Sondek J, Lemmon MA. The Dbs PH domain contributes independently to membrane targeting and regulation of guanine nucleotide-exchange activity. Biochemical Journal 2006, 400: 563-572. PMID: 17007612, PMCID: PMC1698603, DOI: 10.1042/bj20061020.Peer-Reviewed Original ResearchArgos Mutants Define an Affinity Threshold for Spitz Inhibition in Vivo *
Alvarado D, Evans TA, Sharma R, Lemmon MA, Duffy JB. Argos Mutants Define an Affinity Threshold for Spitz Inhibition in Vivo *. Journal Of Biological Chemistry 2006, 281: 28993-29001. PMID: 16870613, DOI: 10.1074/jbc.m603782200.Peer-Reviewed Original Research
2004
Svp1p defines a family of phosphatidylinositol 3,5‐bisphosphate effectors
Dove SK, Piper RC, McEwen RK, Yu JW, King MC, Hughes DC, Thuring J, Holmes AB, Cooke FT, Michell RH, Parker PJ, Lemmon MA. Svp1p defines a family of phosphatidylinositol 3,5‐bisphosphate effectors. The EMBO Journal 2004, 23: 1922-1933. PMID: 15103325, PMCID: PMC404323, DOI: 10.1038/sj.emboj.7600203.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid SequenceAutophagy-Related ProteinsBase SequenceCloning, MolecularEndosomesEscherichia coliGene ComponentsGenetic VectorsGreen Fluorescent ProteinsMembrane ProteinsMolecular Sequence DataPhosphatidylinositol PhosphatesPhosphotransferases (Alcohol Group Acceptor)PlasmidsProtein BindingProtein FoldingProtein TransportRhinovirusSaccharomyces cerevisiaeSaccharomyces cerevisiae ProteinsSequence AlignmentSequence Analysis, DNAVacuolesConceptsFamily of phosphatidylinositolSaccharomyces cerevisiae mutantsDrosophila homologueCerevisiae mutantsMembrane recyclingVesicle recyclingVacuole enlargementVacuole membraneMultivesicular bodiesRelated proteinsLysosomal compartmentMarker proteinsExquisite specificityEffectorsProteinPhosphatidylinositolVacuolesEukaryotesCellsMutantsLocalisesGolgiHomologuesMVBGenesThe p21-activated Protein Kinase-related Kinase Cla4 Is a Coincidence Detector of Signaling by Cdc42 and Phosphatidylinositol 4-Phosphate*
Wild AC, Yu JW, Lemmon MA, Blumer KJ. The p21-activated Protein Kinase-related Kinase Cla4 Is a Coincidence Detector of Signaling by Cdc42 and Phosphatidylinositol 4-Phosphate*. Journal Of Biological Chemistry 2004, 279: 17101-17110. PMID: 14766750, DOI: 10.1074/jbc.m314035200.Peer-Reviewed Original ResearchMeSH KeywordsAllelesAmino Acid SequenceCdc42 GTP-Binding ProteinCell MembraneDose-Response Relationship, DrugEscherichia coliGenotypeGreen Fluorescent ProteinsImmunoblottingKineticsLipid MetabolismLuminescent ProteinsMitosisModels, GeneticMolecular Sequence DataMutationP21-Activated KinasesPhosphatidylinositol PhosphatesPlasmidsPoint MutationProtein BindingProtein Serine-Threonine KinasesProtein Structure, TertiaryRecombinant Fusion ProteinsSaccharomyces cerevisiaeSaccharomyces cerevisiae ProteinsSequence Homology, Amino AcidSignal TransductionSurface Plasmon ResonanceTemperatureConceptsPleckstrin homologyPH domainRho-type GTPase Cdc42P21-activated protein kinaseMitotic exit networkPlasma membrane poolSignal transduction pathwaysPhosphoinositide speciesGolgi poolCell morphogenesisEukaryotic cellsGTPase Cdc42Cdc42 bindingKinase mutantsMammalian cellsCla4Protein kinaseTransduction pathwaysCoincidence detectorMembrane poolPlasma membraneCdc42Kinase activityPI4PBiological processes
2003
Genome-wide analysis of signaling domain function
Yu JW, Lemmon MA. Genome-wide analysis of signaling domain function. Current Opinion In Chemical Biology 2003, 7: 103-109. PMID: 12547434, DOI: 10.1016/s1367-5931(02)00008-x.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid SequenceComputational BiologyGenomeProtein BindingProtein Structure, TertiaryProteinsSignal Transduction
2001
The Single Transmembrane Domains of ErbB Receptors Self-associate in Cell Membranes*
Mendrola JM, Berger MB, King MC, Lemmon MA. The Single Transmembrane Domains of ErbB Receptors Self-associate in Cell Membranes*. Journal Of Biological Chemistry 2001, 277: 4704-4712. PMID: 11741943, DOI: 10.1074/jbc.m108681200.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid MotifsAmino Acid SequenceCell MembraneChloramphenicol O-AcetyltransferaseDimerizationDNA Mutational AnalysisErbB ReceptorsEscherichia coliGenetic VectorsGlutamic AcidHumansLigandsMaltoseModels, MolecularMolecular Sequence DataMutagenesis, Site-DirectedMutationProtein Structure, TertiaryReceptor Protein-Tyrosine KinasesReceptor, ErbB-2Receptor, ErbB-3Receptor, ErbB-4Recombinant Fusion ProteinsSequence Homology, Amino AcidValineConceptsTM domain interactionsTM domainReceptor tyrosine kinasesEpidermal growth factor receptorGrowth factor receptorDomain interactionsSingle transmembrane alpha-helixReceptor dimersTyrosine kinaseExtracellular domainErbB receptor functionEscherichia coli cell membraneSingle transmembrane domainTransmembrane alpha-helixErbB receptorsCell membraneLimited mutational analysisFactor receptorGlutamic acid mutationTransmembrane domainGxxxG motifDomain dimerMutational analysisAlpha-helixErythropoietin receptorAll Phox Homology (PX) Domains from Saccharomyces cerevisiae Specifically Recognize Phosphatidylinositol 3-Phosphate*
Yu J, Lemmon M. All Phox Homology (PX) Domains from Saccharomyces cerevisiae Specifically Recognize Phosphatidylinositol 3-Phosphate*. Journal Of Biological Chemistry 2001, 276: 44179-44184. PMID: 11557775, DOI: 10.1074/jbc.m108811200.Peer-Reviewed Original Research
2000
Crystal Structure of Fibroblast Growth Factor 9 Reveals Regions Implicated in Dimerization and Autoinhibition*
Plotnikov A, Eliseenkova A, Ibrahimi O, Shriver Z, Sasisekharan R, Lemmon M, Mohammadi M. Crystal Structure of Fibroblast Growth Factor 9 Reveals Regions Implicated in Dimerization and Autoinhibition*. Journal Of Biological Chemistry 2000, 276: 4322-4329. PMID: 11060292, DOI: 10.1074/jbc.m006502200.Peer-Reviewed Original ResearchStructural Basis for Discrimination of 3-Phosphoinositides by Pleckstrin Homology Domains
Ferguson K, Kavran J, Sankaran V, Fournier E, Isakoff S, Skolnik E, Lemmon M. Structural Basis for Discrimination of 3-Phosphoinositides by Pleckstrin Homology Domains. Molecular Cell 2000, 6: 373-384. PMID: 10983984, DOI: 10.1016/s1097-2765(00)00037-x.Peer-Reviewed Original ResearchMeSH KeywordsAdaptor Proteins, Signal TransducingAmino Acid SequenceBinding SitesBlood ProteinsCrystallography, X-RayFatty AcidsHydrogen BondingInositol PhosphatesLipoproteinsModels, MolecularMolecular Sequence DataPhosphatidylinositol 3-KinasesPhosphatidylinositolsProtein Structure, SecondarySequence AlignmentSequence Homology, Amino AcidSignal TransductionSrc Homology DomainsSubstrate SpecificityConceptsPleckstrin homology domainPH domainHomology domainDifferent PH domainsPhosphoinositide specificityMembrane recruitmentProtein modulesCellular signalingStructural basisHost proteinsSecond messengerMajor PIAmino acidsX-ray crystal structureProteinDomainPhosphoinositideHead groupsSignalingMessengerBindsCrystal structureRecruitment
1998
The Pleckstrin Homology Domains of Dynamin Isoforms Require Oligomerization for High Affinity Phosphoinositide Binding*
Klein D, Lee A, Frank D, Marks M, Lemmon M. The Pleckstrin Homology Domains of Dynamin Isoforms Require Oligomerization for High Affinity Phosphoinositide Binding*. Journal Of Biological Chemistry 1998, 273: 27725-27733. PMID: 9765310, DOI: 10.1074/jbc.273.42.27725.Peer-Reviewed Original ResearchIdentification and analysis of PH domain‐containing targets of phosphatidylinositol 3‐kinase using a novel in vivo assay in yeast
Isakoff S, Cardozo T, Andreev J, Li Z, Ferguson K, Abagyan R, Lemmon M, Aronheim A, Skolnik E. Identification and analysis of PH domain‐containing targets of phosphatidylinositol 3‐kinase using a novel in vivo assay in yeast. The EMBO Journal 1998, 17: 5374-5387. PMID: 9736615, PMCID: PMC1170863, DOI: 10.1093/emboj/17.18.5374.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid SequenceBlood ProteinsCell MembraneConsensus SequenceConserved SequenceFungal ProteinsModels, MolecularMutationPhosphatidylinositol 3-KinasesPhosphatidylinositol PhosphatesPhosphoproteinsProtein BindingRas ProteinsRecombinant Fusion ProteinsSaccharomyces cerevisiaeSecond Messenger SystemsSequence Homology, Amino AcidConceptsPI3K productsPH domainNon-permissive temperaturePH domain-containing proteinsRas exchange factorK productDomain-containing proteinsPleckstrin homology domainExchange factorHomology domainYeast SaccharomycesNovel cDNAConsensus sequenceFusion proteinSecond messengerCellular responsesPI3KAmino acidsHigh affinityYeastYeast growthProteinPhosphatidylinositolNovel assayPowerful approach
1997
Specific role for the PH domain of dynamin‐1 in the regulation of rapid endocytosis in adrenal chromaffin cells
Artalejo C, Lemmon M, Schlessinger J, Palfrey H. Specific role for the PH domain of dynamin‐1 in the regulation of rapid endocytosis in adrenal chromaffin cells. The EMBO Journal 1997, 16: 1565-1574. PMID: 9130701, PMCID: PMC1169760, DOI: 10.1093/emboj/16.7.1565.Peer-Reviewed Original ResearchMeSH KeywordsAdrenal MedullaAmino Acid SequenceAnimalsBlood ProteinsCattleChromaffin CellsDynamin IDynaminsEndocytosisGenetic VariationGTP PhosphohydrolasesHumansModels, StructuralMolecular Sequence DataMutagenesis, Site-DirectedPatch-Clamp TechniquesPhosphoproteinsPolymerase Chain ReactionProtein Structure, SecondaryRecombinant ProteinsSequence Homology, Amino AcidConceptsPH domainDynamin 1Rapid endocytosisPleckstrin homology domainAmino acidsDynamin PH domainIsolated PH domainTypes of endocytosisChromaffin cellsHomology domainDynamin 2Mutational studiesEquivalent residuesEndocytotic processDifferent isoformsAdrenal chromaffin cellsEndocytosisDynaminVariable loopScission eventsSpecific roleCellsKey roleDomainIsoformsDimerization of the p185neu transmembrane domain is necessary but not sufficient for transformation
Burke C, Lemmon M, Coren B, Engelman D, Stern D. Dimerization of the p185neu transmembrane domain is necessary but not sufficient for transformation. Oncogene 1997, 14: 687-696. PMID: 9038376, DOI: 10.1038/sj.onc.1200873.Peer-Reviewed Original ResearchConceptsReceptor tyrosine kinasesTransmembrane domainEpidermal growth factor receptorSignal transductionWild-type domainSecond-site mutationsPosition 664Dimerization domainGrowth factor receptorTyrosine kinaseGlycophorin AFactor receptorValine substitutionDimerizationMutationsTransductionGlutamic acidDomainWeak dimerizationMutantsKinaseSignalingProteinEGFChimeras
1996
PH Domains: Diverse Sequences with a Common Fold Recruit Signaling Molecules to the Cell Surface
Lemmon M, Ferguson K, Schlessinger J. PH Domains: Diverse Sequences with a Common Fold Recruit Signaling Molecules to the Cell Surface. Cell 1996, 85: 621-624. PMID: 8646770, DOI: 10.1016/s0092-8674(00)81022-3.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus Statements