An 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 insightsKinomeThe 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