2021
Modulation of Phosphoprotein Activity by Phosphorylation Targeting Chimeras (PhosTACs)
Chen PH, Hu Z, An E, Okeke I, Zheng S, Luo X, Gong A, Jaime-Figueroa S, Crews CM. Modulation of Phosphoprotein Activity by Phosphorylation Targeting Chimeras (PhosTACs). ACS Chemical Biology 2021, 16: 2808-2815. PMID: 34780684, PMCID: PMC10437008, DOI: 10.1021/acschembio.1c00693.Peer-Reviewed Original ResearchConceptsSer/Thr phosphataseChemical biology approachPP2A holoenzymeProtein dephosphorylationBiology approachProtein substratesTranscriptional activationProtein phosphorylationCatalytic subunitCell biologyReporter geneProtein activityRetinoblastoma proteinOff-target effectsCritical proteinsDephosphorylationTernary complexPhosphorylationKinase inhibitorsFOXO3aPROTACsProteinChimerasPhosphataseDrug resistance
2013
Posttranslational protein knockdown coupled to receptor tyrosine kinase activation with phosphoPROTACs
Hines J, Gough JD, Corson TW, Crews CM. Posttranslational protein knockdown coupled to receptor tyrosine kinase activation with phosphoPROTACs. Proceedings Of The National Academy Of Sciences Of The United States Of America 2013, 110: 8942-8947. PMID: 23674677, PMCID: PMC3670320, DOI: 10.1073/pnas.1217206110.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid SequenceAnalysis of VarianceAnimalsChromatography, High Pressure LiquidEnzyme ActivationFemaleGene Knockdown TechniquesHumansImmunoblottingMCF-7 CellsMiceMolecular Sequence DataMolecular StructurePC12 CellsPhosphatidylinositol 3-KinasesPhosphorylationProtein Processing, Post-TranslationalProteolysisRatsReceptor Protein-Tyrosine KinasesReceptor, ErbB-3Receptor, Fibroblast Growth Factor, Type 2Receptor, trkASignal TransductionStreptavidinVon Hippel-Lindau Tumor Suppressor ProteinConceptsGrowth factor receptorProtein knockdownFibroblast growth factor receptor substrateVon Hippel-Lindau proteinSpecific receptor tyrosine kinasesKinase-mediated phosphorylationReceptor tyrosine kinase pathwaysFactor receptorKinase signal pathwayTyrosine kinase activationReceptor tyrosine kinasesTyrosine kinase pathwayConditional degradationPhosphorylation sequenceKinase pathwayReceptor substrateKinase activationNucleic acid-based strategiesLindau proteinTarget protein knockdownSpecific proteinsTyrosine kinaseCell-type selectivityNerve growth factor receptorKnockdown
2001
Cells adapted to the proteasome inhibitor 4-hydroxy- 5-iodo-3-nitrophenylacetyl-Leu-Leu-leucinal-vinyl sulfone require enzymatically active proteasomes for continued survival
Princiotta M, Schubert U, Chen W, Bennink J, Myung J, Crews C, Yewdell J. Cells adapted to the proteasome inhibitor 4-hydroxy- 5-iodo-3-nitrophenylacetyl-Leu-Leu-leucinal-vinyl sulfone require enzymatically active proteasomes for continued survival. Proceedings Of The National Academy Of Sciences Of The United States Of America 2001, 98: 513-518. PMID: 11149939, PMCID: PMC14618, DOI: 10.1073/pnas.98.2.513.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid Chloromethyl KetonesAminopeptidasesAnimalsAntigen PresentationAntigensBoronic AcidsBortezomibCD8-Positive T-LymphocytesCell SurvivalCysteine EndopeptidasesDipeptidyl-Peptidases and Tripeptidyl-PeptidasesDrug ResistanceEndopeptidasesEnzyme ActivationH-2 AntigensLeupeptinsLymphoma, T-CellMiceMultienzyme ComplexesNeoplasm ProteinsOligopeptidesPeptide FragmentsPhenolsProtease InhibitorsProteasome Endopeptidase ComplexProtein Processing, Post-TranslationalPyrazinesSelection, GeneticSerine EndopeptidasesSulfonesThymus NeoplasmsTumor Cells, CulturedTumor Suppressor Protein p53TyramineUbiquitinsConceptsII activityLarge proteolytic complexSpecific proteasome inhibitorInhibitor 4Degradation of p53Ala-AlaProteolytic complexPolyubiquitinated proteinsLeu-LeuProteolytic functionActive proteasomesPrimary proteaseProperties of cellsProteolytic systemProteasomeSpecific inhibitorMajor histocompatibility complexPhe-chloromethylketoneProteasome inhibitors
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 ProteinsExtracellular 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
Purification of a murine protein-tyrosine/threonine kinase that phosphorylates and activates the Erk-1 gene product: relationship to the fission yeast byr1 gene product.
Crews CM, Erikson RL. Purification of a murine protein-tyrosine/threonine kinase that phosphorylates and activates the Erk-1 gene product: relationship to the fission yeast byr1 gene product. Proceedings Of The National Academy Of Sciences Of The United States Of America 1992, 89: 8205-8209. PMID: 1381507, PMCID: PMC49886, DOI: 10.1073/pnas.89.17.8205.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid SequenceAnimalsEnzyme ActivationFungal ProteinsGenesMiceMitogen-Activated Protein Kinase 3Mitogen-Activated Protein KinasesMolecular Sequence DataPeptide FragmentsPhosphorylationPhosphoserinePhosphothreoninePhosphotyrosineProtein KinasesRecombinant ProteinsSequence AlignmentTyrosineConceptsGene productsProtein kinaseSerine/threonine phosphatase 2AMyelin basic protein kinaseProtein tyrosine phosphatase 1B.MAPK/ERK kinaseSignal transduction mechanismsPossible signal transduction mechanismsERK-1 proteinSte7 genePhosphatase 2AThreonine kinaseERK kinaseERK-1Tyrosine residuesSequence analysisKinaseTransduction mechanismsMEKTrypsin digestionProteinByr1PurificationGenesLesser extent