Recent estimates of the human proteome suggest there are ∼20,000 protein-coding genes, the protein products of which contain >145,000 phosphosites. Unfortunately, in-depth examination of the human phosphoproteome has outpaced the ability to annotate the kinases that mediate these post-translational modifications. To obtain actionable information about phosphorylation-driven signaling cascades, it is essential to identify the kinases responsible for phosphorylating sites that differ across disease states. To fill in these gaps we have developed an unbiased, chemoproteomic approach for identifying high-confidence kinase-substrate interactions with phosphosite specificity. Using this assay, we uncovered the role of cyclin-dependent kinase 4 (CDK4), a clinically validated kinase important for cell-cycle progression, in regulating cap-dependent translation via phosphorylation of the tumor suppressor 4E-BP1. The discovery of this signaling axis sheds light on the mechanisms by which CDK4/6 inhibitors control cell proliferation and constitutes a successful example of kinase discovery using an activity-based, kinase-directed probe.
Pubmed ID: 31056462 RIS Download
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This polyclonal targets IgG
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View all literature mentionsThis polyclonal secondary targets IgG (H+L)
View all literature mentionsThis polyclonal secondary targets IgG (H+L)
View all literature mentionsThis monoclonal targets FLAG
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View all literature mentionsThis monoclonal targets Rb1
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View all literature mentionsThis monoclonal targets 4E-BP1 (53H11) Rabbit mAb
View all literature mentionsThis polyclonal targets SAPK/JNK
View all literature mentionsThis polyclonal targets Phospho-4E-BP1 (Ser65)
View all literature mentionsThis monoclonal targets 4E-BP1, phospho (Thr37 / Thr46)
View all literature mentionsThis polyclonal targets Phospho-4E-BP1 (Thr70)
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View all literature mentionsThis polyclonal targets Phospho-S6 Ribosomal Protein (Ser240/244)
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View all literature mentionsThis polyclonal targets eIF4G
View all literature mentionsThis monoclonal targets Cyclin D2 (D52F9) Rabbit mAb
View all literature mentionsThis monoclonal targets DYKDDDDK Tag
View all literature mentionsThis monoclonal targets Cyclin D1
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View all literature mentionsThis monoclonal targets CDK6
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