2001
The anti-inflammatory natural product parthenolide from the medicinal herb Feverfew directly binds to and inhibits IκB kinase
Kwok B, Koh B, Ndubuisi M, Elofsson M, Crews C. The anti-inflammatory natural product parthenolide from the medicinal herb Feverfew directly binds to and inhibits IκB kinase. Cell Chemical Biology 2001, 8: 759-766. PMID: 11514225, DOI: 10.1016/s1074-5521(01)00049-7.Peer-Reviewed Original ResearchConceptsAnti-inflammatory activityHerb feverfewPro-inflammatory signaling pathwaysDirect molecular targetVivo anti-inflammatory activityAnti-inflammatory propertiesAnti-inflammatory agentsCytokine-mediated stimulationCytokine-mediated signalingIkappaB kinase betaSesquiterpene lactone parthenolidePharmaceutical interventionsIκB kinaseMolecular targetsNatural product parthenolideKinase betaParthenolideCysteine 179Signaling pathwaysPossible molecular basisIntracellular signaling processesAttractive targetIKK complexMolecular mechanismsAlpha-methylene gamma-lactone moiety
1996
Deciphering isozyme function: exploring cell biology with chemistry in the post-genomic era
Crews C. Deciphering isozyme function: exploring cell biology with chemistry in the post-genomic era. Cell Chemical Biology 1996, 3: 961-965. PMID: 9000005, DOI: 10.1016/s1074-5521(96)90162-3.Peer-Reviewed Original Research
1993
Raf-1 forms a stable complex with Mek1 and activates Mek1 by serine phosphorylation.
Huang W, Alessandrini A, Crews CM, Erikson RL. Raf-1 forms a stable complex with Mek1 and activates Mek1 by serine phosphorylation. Proceedings Of The National Academy Of Sciences Of The United States Of America 1993, 90: 10947-10951. PMID: 8248196, PMCID: PMC47898, DOI: 10.1073/pnas.90.23.10947.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsEnzyme ActivationIn Vitro TechniquesMacromolecular SubstancesMAP Kinase Kinase 1MiceMitogen-Activated Protein Kinase KinasesPhosphorylationPhosphoserineProtein BindingProtein Serine-Threonine KinasesProtein-Tyrosine KinasesProto-Oncogene ProteinsProto-Oncogene Proteins c-rafRecombinant ProteinsReconstitution of the Raf-1-MEK-ERK signal transduction pathway in vitro.
Macdonald SG, Crews CM, Wu L, Driller J, Clark R, Erikson RL, McCormick F. Reconstitution of the Raf-1-MEK-ERK signal transduction pathway in vitro. Molecular And Cellular Biology 1993, 13: 6615-6620. PMID: 8413257, PMCID: PMC364724, DOI: 10.1128/mcb.13.11.6615.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBaculoviridaeCell LineCloning, MolecularGenes, rasGenes, srcHumansMAP Kinase Kinase 1Mitogen-Activated Protein Kinase KinasesMothsMutagenesis, Site-DirectedPhosphorylationPolymerase Chain ReactionProtein Serine-Threonine KinasesProtein-Tyrosine KinasesProto-Oncogene ProteinsProto-Oncogene Proteins c-rafProto-Oncogene Proteins p21(ras)Recombinant ProteinsSignal TransductionTransfectionConceptsRaf-1V-SrcV-rasSf9 cellsGlutathione S-transferase fusion proteinS-transferase fusion proteinSerine/threonine kinaseProtein kinase C phosphorylationKinase-inactive versionERK signal transduction pathwayKinase-inactive mutantRaf-1 phosphorylationKinase C phosphorylationSignal transduction pathwaysRaf-1-MEKActivation of MEKTyrosine kinase oncogenesProtein kinase CAutokinase activityFunction upstreamThreonine kinaseDirect substrateMEK activationTransduction pathwaysC phosphorylationMEK2 is a kinase related to MEK1 and is differentially expressed in murine tissues.
Brott BK, Alessandrini A, Largaespada DA, Copeland NG, Jenkins NA, Crews CM, Erikson RL. MEK2 is a kinase related to MEK1 and is differentially expressed in murine tissues. Molecular Cancer Research 1993, 4: 921-9. PMID: 8297798.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid SequenceAmino AcidsAnimalsAnimals, NewbornBase SequenceBrainChromosome MappingCloning, MolecularFemaleGene Expression RegulationMaleMAP Kinase Kinase 1MAP Kinase Kinase 2MiceMitogen-Activated Protein Kinase KinasesMolecular Sequence DataNucleic Acid HybridizationProtein Serine-Threonine KinasesProtein-Tyrosine KinasesRecombinant ProteinsRNA, MessengerSequence AnalysisConceptsERK-1Dual-specificity kinaseMurine chromosome 9Substantial sequence homologyErk/MAPMultigene familyLow expression levelsMEK2 proteinsAdult mouse brainSequence homologyAmino terminusDifferent genesERK-2MEK2MEK1Northern analysisChromosome 9Complementary DNAMurine tissuesExpression levelsKinaseExtracellular signals and reversible protein phosphorylation: What to Mek of it all
Crews C, Erikson R. Extracellular signals and reversible protein phosphorylation: What to Mek of it all. Cell 1993, 74: 215-217. PMID: 8343948, DOI: 10.1016/0092-8674(93)90411-i.Peer-Reviewed Original Research
1992
The Primary Structure of MEK, a Protein Kinase that Phosphorylates the ERK Gene Product
Crews C, Alessandrini A, Erikson R. The Primary Structure of MEK, a Protein Kinase that Phosphorylates the ERK Gene Product. Science 1992, 258: 478-480. PMID: 1411546, DOI: 10.1126/science.1411546.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid SequenceAnimalsBase SequenceCalcium-Calmodulin-Dependent Protein KinasesGene ExpressionMAP Kinase Kinase 1MiceMitogen-Activated Protein Kinase KinasesMolecular Sequence DataPhosphorylationProtein KinasesProtein Serine-Threonine KinasesProteinsProtein-Tyrosine KinasesRNA, MessengerSequence AlignmentConceptsExtracellular signal-regulated kinaseProtein kinaseMAP kinaseGene productsCritical protein kinaseSignal-regulated kinaseComplementary DNA sequenceMEK genesExtracellular signalsERK kinaseMultiple biochemical signalsDNA sequencesBiochemical signalsPrimary structureKinaseAmino acidsEnzymatic activityGenesMurine brainSequenceSchizosaccharomycesMEK1MEKThreonineProtein
1991
Mouse Erk-1 gene product is a serine/threonine protein kinase that has the potential to phosphorylate tyrosine.
Crews CM, Alessandrini AA, Erikson RL. Mouse Erk-1 gene product is a serine/threonine protein kinase that has the potential to phosphorylate tyrosine. Proceedings Of The National Academy Of Sciences Of The United States Of America 1991, 88: 8845-8849. PMID: 1717989, PMCID: PMC52607, DOI: 10.1073/pnas.88.19.8845.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid SequenceAnimalsBase SequenceBlotting, WesternCalcium-Calmodulin-Dependent Protein KinasesCloning, MolecularMiceMolecular Sequence DataMolecular WeightMyelin Basic ProteinOligonucleotidesPhosphoprotein PhosphatasesPhosphoproteinsPhosphotyrosinePolymerase Chain ReactionProtein KinasesProtein Phosphatase 2Protein Serine-Threonine KinasesRecombinant ProteinsTyrosineConceptsSerine/threonine protein kinaseERK-1Serine/threonine kinaseRibosomal protein S6 kinaseSubstrate phosphorylation sitesThreonine protein kinaseProtein S6 kinaseSame substrate specificityPhosphatase 2AThreonine residuesThreonine kinaseActive kinasePhosphorylation sitesERK1 proteinS6 kinaseProtein kinaseSequence dataBacterial expressionSubstrate specificityGene productsKinase activityPhosphatase 1BKinaseRat cellsProtein