2025
Cancer hotspot mutations rewire ERK2 specificity by selective exclusion of docking interactions
Torres Robles J, Stiegler A, Boggon T, Turk B. Cancer hotspot mutations rewire ERK2 specificity by selective exclusion of docking interactions. Journal Of Biological Chemistry 2025, 301: 108348. PMID: 40015635, DOI: 10.1016/j.jbc.2025.108348.Peer-Reviewed Original ResearchShort linear motifsCancer hotspot mutationsLinear motifsERK substratesYeast two-hybrid libraryHotspot mutationsTwo-hybrid libraryCancer-associated mutantsDocking interactionsWild-type ERK2Cancer-associated mutationsDocking motifBinding sequenceKinase ERK2Co-crystal structureMutant formsERK2 mutantsDisordered regionsERK2MotifStructural rationalePeptide bindingMutationsWT kinasePeptide fragments
2023
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 interactionProteome-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 librariesMKK6ProteomeMKK7
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