Featured Publications
Distinct functional constraints driving conservation of the cofilin N-terminal regulatory tail
Sexton J, Potchernikov T, Bibeau J, Casanova-Sepúlveda G, Cao W, Lou H, Boggon T, De La Cruz E, Turk B. Distinct functional constraints driving conservation of the cofilin N-terminal regulatory tail. Nature Communications 2024, 15: 1426. PMID: 38365893, PMCID: PMC10873347, DOI: 10.1038/s41467-024-45878-9.Peer-Reviewed Original ResearchConceptsN-terminal regionActin bindingSequence requirementsLIM kinaseAnalysis of individual variantsInactivates cofilinS. cerevisiaeRegulatory tailFamily proteinsActin depolymerizationPhosphorylation sitesKinase recognitionSequence variantsInhibitory phosphorylationCofilinN-terminusIndividual variantsFunctional constraintsActinDisordered sequencesPhosphorylationSequenceBiochemical analysisSequence constraintsKinaseAn atlas of substrate specificities for the human serine/threonine kinome
Johnson J, Yaron T, Huntsman E, Kerelsky A, Song J, Regev A, Lin T, Liberatore K, Cizin D, Cohen B, Vasan N, Ma Y, Krismer K, Robles J, van de Kooij B, van Vlimmeren A, Andrée-Busch N, Käufer N, Dorovkov M, Ryazanov A, Takagi Y, Kastenhuber E, Goncalves M, Hopkins B, Elemento O, Taatjes D, Maucuer A, Yamashita A, Degterev A, Uduman M, Lu J, Landry S, Zhang B, Cossentino I, Linding R, Blenis J, Hornbeck P, Turk B, Yaffe M, Cantley L. An atlas of substrate specificities for the human serine/threonine kinome. Nature 2023, 613: 759-766. PMID: 36631611, PMCID: PMC9876800, DOI: 10.1038/s41586-022-05575-3.Peer-Reviewed Original ResearchConceptsSer/ThrHuman Ser/ThrSubstrate specificityPhosphorylation eventsProtein serine/threonine kinaseWidespread post-translational modificationSerine/threonine kinasePutative protein kinaseSubstrate sequence specificityIntrinsic substrate specificityPost-translational modificationsThreonine phosphorylationGenetic perturbationsThreonine kinasePhosphorylation sitesHuman genomeProtein phosphorylationProtein kinaseSequence specificityBiological pathwaysHuman diseasesNegative selectivityKinaseUnexpected insightsKinomeProteome-wide screening for mitogen-activated protein kinase docking motifs and interactors
Shi G, Song C, Torres Robles J, Salichos L, Lou H, Lam T, Gerstein M, Turk B. Proteome-wide screening for mitogen-activated protein kinase docking motifs and interactors. Science Signaling 2023, 16: eabm5518. PMID: 36626580, PMCID: PMC9995140, DOI: 10.1126/scisignal.abm5518.Peer-Reviewed Original ResearchConceptsMitogen-activated protein kinaseDocking motifSequence motifsDocking sequenceShort linear sequence motifsLinear sequence motifsSubstrate recruitmentHuman proteomeProtein kinaseCatalytic cleftExchange mutantsEssential functionsCultured cellsScreening pipelineWide screeningInteractorsMotifSequenceLimited repertoireSelective bindingInteractomeCombinatorial librariesMKK6ProteomeMKK7Homing in: Mechanisms of Substrate Targeting by Protein Kinases
Miller CJ, Turk BE. Homing in: Mechanisms of Substrate Targeting by Protein Kinases. Trends In Biochemical Sciences 2018, 43: 380-394. PMID: 29544874, PMCID: PMC5923429, DOI: 10.1016/j.tibs.2018.02.009.Peer-Reviewed Original ResearchConceptsProtein kinaseReversible post-translational modificationKinase substrate specificityCellular signaling networksPost-translational modificationsSimilar catalytic domainsMode of regulationSignaling outputsSubstrate repertoireSubstrate targetingSignaling networksPhosphorylation sitesProtein phosphorylationCatalytic domainSubstrate specificityKinaseCell behaviorEukaryotesRecent progressPhosphorylationAnticancer drugsSitesRegulationMechanismTargeting
2022
Tousled-like kinase 2 targets ASF1 histone chaperones through client mimicry
Simon B, Lou HJ, Huet-Calderwood C, Shi G, Boggon TJ, Turk BE, Calderwood DA. Tousled-like kinase 2 targets ASF1 histone chaperones through client mimicry. Nature Communications 2022, 13: 749. PMID: 35136069, PMCID: PMC8826447, DOI: 10.1038/s41467-022-28427-0.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid MotifsAmino Acid SequenceCatalytic DomainCell Cycle ProteinsConserved SequenceCrystallography, X-RayHistonesHumansMolecular ChaperonesMolecular Docking SimulationMolecular MimicryMutagenesisPeptide LibraryPhosphorylationProtein KinasesRecombinant ProteinsSubstrate SpecificityConceptsTousled-like kinaseDNA replication-coupled nucleosome assemblyNuclear serine-threonine kinaseReplication-coupled nucleosome assemblyHistone chaperone proteinsGlobular N-terminal domainProper cell divisionPhosphorylation site motifsSerine-threonine kinaseShort sequence motifsAsf1 histone chaperonesC-terminal tailN-terminal domainHistone chaperonesGenome maintenanceNucleosome assemblySequence motifsChaperone proteinsNon-catalytic interactionsCatalytic domainCell divisionSite motifN-terminusStringent selectivityCell growth
2021
PPP6C negatively regulates oncogenic ERK signaling through dephosphorylation of MEK
Cho E, Lou HJ, Kuruvilla L, Calderwood DA, Turk BE. PPP6C negatively regulates oncogenic ERK signaling through dephosphorylation of MEK. Cell Reports 2021, 34: 108928. PMID: 33789117, PMCID: PMC8068315, DOI: 10.1016/j.celrep.2021.108928.Peer-Reviewed Original ResearchConceptsProtein kinase cascadeCore oncogenic pathwaysKey negative regulatorOncogenic ERKERK pathway activationCrosstalk regulationCentral kinaseKinase cascadePhosphorylation sitesRegulatory subunitRaf-MEKNegative regulatorERK pathwayDrug targetsOncogenic pathwaysMEKMEK inhibitorsDephosphorylationPathway activationPPP6CPhosphatasePathwayERKHyperphosphorylationCascade