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 ResearchMeSH KeywordsAmino Acid SequenceCatalysisGlycineHumansModels, MolecularMolecular Sequence DataReceptor Protein-Tyrosine KinasesSequence Homology, Amino AcidSignal TransductionWnt ProteinsConceptsWeak kinase activityKinase activitySignificant kinase activityReceptor tyrosine kinasesPseudokinase domainHuman proteomeProtein kinaseImportant residuesWnt receptorsTyrosine kinaseEGFR familyKinaseFunctional studiesRTKPseudokinasesPseudokinaseProteomeReceptorsWntNew lightErbB3MutationsResiduesActivityRecent work
2011
Molecular dynamics analysis of conserved hydrophobic and hydrophilic bond-interaction networks in ErbB family kinases
Shih AJ, Telesco SE, Choi SH, Lemmon MA, Radhakrishnan R. Molecular dynamics analysis of conserved hydrophobic and hydrophilic bond-interaction networks in ErbB family kinases. Biochemical Journal 2011, 436: 241-251. PMID: 21426301, PMCID: PMC3138537, DOI: 10.1042/bj20101791.Peer-Reviewed Original ResearchConceptsErbB familyDifferent molecular contextsIntracellular kinase domainImportant regulatory elementsSrc kinase HckReceptor tyrosine kinasesHomologous receptor tyrosine kinasesSequence similarityKinase domainRegulatory elementsDimer interfaceSubdomain motionsInactive conformationKey residuesEGFR activationMolecular contextTyrosine kinasePresent molecular dynamics studyBond networkActive conformationConformational statesKinaseErbB kinasesMolecular dynamics analysisSalt bridge
2009
A possible effector role for the pleckstrin homology (PH) domain of dynamin
Bethoney KA, King MC, Hinshaw JE, Ostap EM, Lemmon MA. A possible effector role for the pleckstrin homology (PH) domain of dynamin. Proceedings Of The National Academy Of Sciences Of The United States Of America 2009, 106: 13359-13364. PMID: 19666604, PMCID: PMC2720410, DOI: 10.1073/pnas.0906945106.Peer-Reviewed Original ResearchConceptsPleckstrin homology domainHomology domainPH domainAbility of dynaminLarge GTPase dynaminPH domain mutationsPhosphoinositide-containing membranesGTPase dynaminDynamin functionVesicle scissionMembrane scissionDynamin helixDynamin assemblyTargeting roleDynamin oligomersDynamin 1Possible effector roleAnimal cellsBisphosphate moleculesActin polymerizationDynaminClathrinDomain mutationsPhosphoinositideEndocytosis
2006
Argos 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
Genome-Wide Analysis of Membrane Targeting by S. cerevisiae Pleckstrin Homology Domains
Yu JW, Mendrola JM, Audhya A, Singh S, Keleti D, DeWald DB, Murray D, Emr SD, Lemmon MA. Genome-Wide Analysis of Membrane Targeting by S. cerevisiae Pleckstrin Homology Domains. Molecular Cell 2004, 13: 677-688. PMID: 15023338, DOI: 10.1016/s1097-2765(04)00083-8.Peer-Reviewed Original ResearchMeSH KeywordsBinding SitesBlood ProteinsCalcium-Binding ProteinsCell MembraneCytoskeletal ProteinsGene Expression Regulation, FungalGenome, FungalPhosphatidylinositolsPhosphoproteinsProtein BindingProtein Structure, TertiarySaccharomyces cerevisiaeSaccharomyces cerevisiae ProteinsSequence Homology, Amino AcidConceptsPH domain bindsMembrane targetingPH domainDomain bindsPhosphoinositide-dependent mannerS. cerevisiae genomeSmall protein modulesPleckstrin homology domainProteome-wide analysisFunction of proteinsMembrane recruitmentCerevisiae genomePhosphoinositide bindingPleckstrin homologyHomology domainProtein modulesWide analysisSubcellular localizationHost proteinsBindsLittle specificityPhosphoinositideProteinHigh affinityCommon domainThe 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
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
Specificity and Promiscuity in Phosphoinositide Binding by Pleckstrin Homology Domains*
Kavran J, Klein D, Lee A, Falasca M, Isakoff S, Skolnik E, Lemmon M. Specificity and Promiscuity in Phosphoinositide Binding by Pleckstrin Homology Domains*. Journal Of Biological Chemistry 1998, 273: 30497-30508. PMID: 9804818, DOI: 10.1074/jbc.273.46.30497.Peer-Reviewed Original ResearchConceptsPleckstrin homology domainPH domainGrp1 PH domainD-myo-inositolParticular phosphoinositidesPhosphoinositide bindingHomology domainDependent membrane recruitmentDifferent PH domainsPH domain bindsSmall protein modulesSoluble inositol phosphatesMembrane recruitmentDomain bindsProtein modulesSpecific phosphoinositideMammalian cellsPlasma membraneSingle speciesAbundant speciesMultiple phosphoinositidesCellular membranesPhosphoinositidePI 3Clear specificityThe 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
Identification of the Binding Site for Acidic Phospholipids on the PH Domain of Dynamin: Implications for Stimulation of GTPase Activity
Zheng J, Cahill S, Lemmon M, Fushman D, Schlessinger J, Cowburn D. Identification of the Binding Site for Acidic Phospholipids on the PH Domain of Dynamin: Implications for Stimulation of GTPase Activity. Journal Of Molecular Biology 1996, 255: 14-21. PMID: 8568861, DOI: 10.1006/jmbi.1996.0002.Peer-Reviewed Original ResearchMeSH KeywordsBinding SitesBlood ProteinsDynaminsGTP PhosphohydrolasesHumansKineticsMagnetic Resonance SpectroscopyModels, MolecularPhosphatidic AcidsPhosphatidylinositol 4,5-DiphosphatePhosphatidylinositol PhosphatesPhosphoproteinsProtein ConformationSequence Homology, Amino AcidSpectrometry, FluorescenceConceptsDynamin PH domainPH domainMembrane associationGTPase activityGuanine nucleotide exchange factorsNucleotide exchange factorsPleckstrin homology domainAcidic phospholipidsBinding of phospholipidsHomology domainExchange factorHuman dynaminGTP hydrolysisDynaminLipid head groupsLigand interactionsGTPaseBinding sitesPhosphatidylinositolSpecific sitesProteinPhospholipidsRelative affinityBindingDomain
1995
Structure of the high affinity complex of inositol trisphosphate with a phospholipase C pleckstrin homology domain
Ferguson K, Lemmon M, Schlessinger J, Sigler P. Structure of the high affinity complex of inositol trisphosphate with a phospholipase C pleckstrin homology domain. Cell 1995, 83: 1037-1046. PMID: 8521504, DOI: 10.1016/0092-8674(95)90219-8.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid SequenceAnimalsBinding SitesBlood ProteinsCrystallography, X-RayInositol 1,4,5-TrisphosphateIsoenzymesMolecular ConformationMolecular Sequence DataPhospholipase C gammaPhosphoproteinsProtein ConformationRatsSequence AlignmentSequence Homology, Amino AcidSpectrinType C PhospholipasesConceptsPleckstrin homology domainHigh-affinity complexHomology domainPH domainPhospholipase C-delta 1C-delta 1Affinity complexHead group specificityMembrane targetingLoss of functionSignaling proteinsDomain foldsMutational changesBtk mutantsRegulatory functionsAmino acidsX-ray crystal structureBeta 2Beta 1/beta 2InositolDomainMutantsComplexesProteinTrisphosphateScratching the surface with the PH domain
Ferguson K, Lemmon M, Sigler P, Schlessinger J. Scratching the surface with the PH domain. Nature Structural & Molecular Biology 1995, 2: 715-718. PMID: 7552736, DOI: 10.1038/nsb0995-715.Commentaries, Editorials and Letters
1994
Crystal structure at 2.2 Å resolution of the pleckstrin homology domain from human dynamin
Ferguson K, Lemmon M, Schlessinger J, Sigler P. Crystal structure at 2.2 Å resolution of the pleckstrin homology domain from human dynamin. Cell 1994, 79: 199-209. PMID: 7954789, DOI: 10.1016/0092-8674(94)90190-2.Peer-Reviewed Original ResearchThermodynamic studies of tyrosyl-phosphopeptide binding to the SH2 domain of p56lck.
Lemmon MA, Ladbury JE. Thermodynamic studies of tyrosyl-phosphopeptide binding to the SH2 domain of p56lck. Biochemistry 1994, 33: 5070-6. PMID: 7513553, DOI: 10.1021/bi00183a010.Peer-Reviewed Original ResearchAmino Acid SequenceAnimalsBinding SitesCalorimetryCloning, MolecularConserved SequenceErbB ReceptorsEscherichia coliLymphocyte Specific Protein Tyrosine Kinase p56(lck)LymphocytesMolecular Sequence DataPeptide FragmentsPhosphopeptidesPhosphotyrosineProtein-Tyrosine KinasesRecombinant ProteinsSequence Homology, Amino AcidTyrosine