Linear motif specificity in signaling through p38α and ERK2 mitogen–activated protein kinases
Robles J, Lou H, Shi G, Pan P, Turk B. Linear motif specificity in signaling through p38α and ERK2 mitogen–activated protein kinases. Proceedings Of The National Academy Of Sciences Of The United States Of America 2023, 120: e2316599120. PMID: 37988460, PMCID: PMC10691213, DOI: 10.1073/pnas.2316599120.Peer-Reviewed Original ResearchConceptsExtracellular signal-regulated kinase 2Docking motifERK2 mitogen-activated protein kinaseSignal-regulated kinase 2Protein kinase cascadeMitogen-activated protein kinaseFull-length proteinMAPK substratesEukaryotic cellsKinase cascadeMAPK networkLinear motifsProtein kinaseMotif specificityProteomic librariesDocking siteAcidic residuesKinase 2Diverse stimuliCellular responsesP38αDocking interfaceHigh net chargeMotifSelective interactionAn 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