ArticleACS chemical biology2014
Divergent modulation of Src-family kinase regulatory interactions with ATP-competitive inhibitors.
Article in ACS chemical biology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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
18 citing papers in PubMed, 27 citations in OpenAlex.
- Article
- Profiling of drug resistance in Src kinase at scale uncovers a regulatory network coupling autoinhibition and catalytic domain dynamics.Cell chemical biology · 2024Article
- A back-door insight into the modulation of Src kinase activity by the polyamine spermidine.eLife · 2023Article
- Discovery of a tetrahydroisoquinoline-based CDK9-cyclin T1 protein-protein interaction inhibitor as an anti-proliferative and anti-migration agent against triple-negative breast cancer cells.Genes & diseases · 2022Article
- Conformation-tunable ATP-competitive kinase inhibitors.Chemical communications (Cambridge, England) · 2022Article
- Differential impact of BTK active site inhibitors on the conformational state of full-length BTK.eLife · 2020Article
- Parallel Chemoselective Profiling for Mapping Protein Structure.Cell chemical biology · 2020Article
- How ATP-Competitive Inhibitors Allosterically Modulate Tyrosine Kinases That Contain a Src-like Regulatory Architecture.ACS chemical biology · 2020Article
- Chemoproteomic Method for Profiling Inhibitor-Bound Kinase Complexes.Journal of the American Chemical Society · 2019Article
- Selective Proteolysis to Study the Global Conformation and Regulatory Mechanisms of c-Src Kinase.ACS chemical biology · 2019Article
- Targeting Dynamic ATP-Binding Site Features Allows Discrimination between Highly Homologous Protein Kinases.ACS chemical biology · 2019Article
- A Combined Approach Reveals a Regulatory Mechanism Coupling Src's Kinase Activity, Localization, and Phosphotransferase-Independent Functions.Molecular cell · 2019Article
- Allosteric Modulation of JNK Docking Site Interactions with ATP-Competitive Inhibitors.Biochemistry · 2018Article
- Survey of solution dynamics in Src kinase reveals allosteric cross talk between the ligand binding and regulatory sites.Nature communications · 2017Article
- Structural and Functional Analysis of the Allosteric Inhibition of IRE1α with ATP-Competitive Ligands.ACS chemical biology · 2016Article
- Targeting transcription is no longer a quixotic quest.Nature chemical biology · 2015Article
- Structure of mycobacterial maltokinase, the missing link in the essential GlgE-pathway.Scientific reports · 2015Article
- SH2-catalytic domain linker heterogeneity influences allosteric coupling across the SFK family.Biochemistry · 2014Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
Multidomain protein kinases, central controllers of signal transduction, use regulatory domains to modulate catalytic activity in a complex cellular environment. Additionally, these domains regulate noncatalytic functions, including cellular localization and protein-protein interactions. Src-family kinases (SFKs) are promising therapeutic targets for a number of diseases and are an excellent model for studying the regulation of multidomain kinases. Here, we demonstrate that the regulatory domains of the SFKs Src and Hck are divergently affected by ligands that stabilize two distinct inactive ATP-binding site conformations. Conformation-selective, ATP-competitive inhibitors differentially modulate the ability of the SH3 and SH2 domains of Src and Hck to engage in intermolecular interactions and the ability of the kinase-inhibitor complex to undergo post-translational modification by effector enzymes. This surprising divergence in regulatory domain behavior by two classes of inhibitors that each stabilize inactive ATP-binding site conformations is found to occur through perturbation or stabilization of the αC helix. These studies provide insight into how conformation-selective, ATP-competitive inhibitors can be designed to modulate domain interactions and post-translational modifications distal to the ATP-binding site of kinases.
Indexed as
Identifiers
What OpenQuestion holds
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.