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 insightsKinomeHoming 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 drugsSitesRegulationMechanismTargetingThe intrinsic substrate specificity of the human tyrosine kinome
Yaron-Barir T, Joughin B, Huntsman E, Kerelsky A, Cizin D, Cohen B, Regev A, Song J, Vasan N, Lin T, Orozco J, Schoenherr C, Sagum C, Bedford M, Wynn R, Tso S, Chuang D, Li L, Li S, Creixell P, Krismer K, Takegami M, Lee H, Zhang B, Lu J, Cossentino I, Landry S, Uduman M, Blenis J, Elemento O, Frame M, Hornbeck P, Cantley L, Turk B, Yaffe M, Johnson J. The intrinsic substrate specificity of the human tyrosine kinome. Nature 2024, 629: 1174-1181. PMID: 38720073, PMCID: PMC11136658, DOI: 10.1038/s41586-024-07407-y.Peer-Reviewed Original ResearchIntrinsic substrate specificityTyr kinasesTyr sitesSequence specificityProtein Tyr kinasesSubstrate sequence specificitySites of phosphorylationPhosphorylation of proteinsMulticellular eukaryotesMetazoan organismsMotif preferencesPhosphoproteomic datasetsSubstrate sequenceTyrosine (Tyr) residuesKinase specificityPattern of residuesSubstrate specificitySignaling networksYears of evolutionPeptide arraysTyrosine kinomeAnti-cancer drugsOncogenic variantsTyr residuesKinase