ArticleCell2015
Unmasking determinants of specificity in the human kinome.
Article in Cell, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
40 citing papers in PubMed, 89 citations in OpenAlex.
- A Constellation of Fluorescent Biosensors to Illuminate the Galaxy of Protein Kinases.Chembiochem : a European journal of chemical biology · 2026Review
- The pathogenic T42A mutation in SHP2 rewires the interaction specificity of its N-terminal regulatory domain.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- The pathogenic T42A mutation in SHP2 rewires the interaction specificity of its N-terminal regulatory domain.bioRxiv : the preprint server for biology · 2024Article
- Article
- Deep Hidden Physics Modeling of Cell Signaling Networks.Current genomics · 2021Article
- Prediction of Protein Sites and Physicochemical Properties Related to Functional Specificity.Bioengineering (Basel, Switzerland) · 2021Article
- Evolution of CDK1 Paralog Specializations in a Lineage With Fast Developing Planktonic Embryos.Frontiers in cell and developmental biology · 2021Article
- A Degenerate Peptide Library Approach to Reveal Sequence Determinants of Methyllysine-Driven Protein Interactions.Frontiers in cell and developmental biology · 2020Article
- Type 2 Diabetes, Obesity, and Cancer Share Some Common and Critical Pathways.Frontiers in oncology · 2020Review
- Mass Spectrometry-Based Discovery ofMass spectrometry (Tokyo, Japan) · 2020Article
- A Structurally-Validated Multiple Sequence Alignment of 497 Human Protein Kinase Domains.Scientific reports · 2019Article
- Evolution of protein kinase substrate recognition at the active site.PLoS biology · 2019Article
- Comprehensive profiling of the STE20 kinase family defines features essential for selective substrate targeting and signaling output.PLoS biology · 2019Article
- Kinome-wide identification of phosphorylation networks in eukaryotic proteomes.Bioinformatics (Oxford, England) · 2019Article
- Understanding molecular mechanisms in cell signaling through natural and artificial sequence variation.Nature structural & molecular biology · 2019Review
- Article
- Kinase Substrate Profiling Using a Proteome-wide Serine-Oriented Human Peptide Library.Biochemistry · 2018Article
- Classifying tumors by supervised network propagation.Bioinformatics (Oxford, England) · 2018Article
- In Vivo Phosphoproteome Analysis Reveals Kinome Reprogramming in Hepatocellular Carcinoma.Molecular & cellular proteomics : MCP · 2018Article
- Homing in: Mechanisms of Substrate Targeting by Protein Kinases.Trends in biochemical sciences · 2018Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 4 institutions in 3 countries.
Funding
Abstract
Protein kinases control cellular responses to environmental cues by swift and accurate signal processing. Breakdowns in this high-fidelity capability are a driving force in cancer and other diseases. Thus, our limited understanding of which amino acids in the kinase domain encode substrate specificity, the so-called determinants of specificity (DoS), constitutes a major obstacle in cancer signaling. Here, we systematically discover several DoS and experimentally validate three of them, named the αC1, αC3, and APE-7 residues. We demonstrate that DoS form sparse networks of non-conserved residues spanning distant regions. Our results reveal a likely role for inter-residue allostery in specificity and an evolutionary decoupling of kinase activity and specificity, which appear loaded on independent groups of residues. Finally, we uncover similar properties driving SH2 domain specificity and demonstrate how the identification of DoS can be utilized to elucidate a greater understanding of the role of signaling networks in cancer (Creixell et al., 2015 [this issue of Cell]).
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.