ArticlePLoS computational biology2012
Allosteric communication across the native and mutated KIT receptor tyrosine kinase.
Article in PLoS computational biology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
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Who cites it
34 citing papers in PubMed, 64 citations in OpenAlex.
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- Mean-Field Coupling Between Local Interactions in Proteins in Relation to Chirality, Secondary, and Supersecondary Structure Formation, and Allostery.Methods in molecular biology (Clifton, N.J.) · 2025Article
- The FLT3American journal of hematology · 2023Article
- Origin of Correlations between Local Conformational States of Consecutive Amino Acid Residues and Their Role in Shaping Protein Structures and in Allostery.The journal of physical chemistry. B · 2022Article
- The Inherent Coupling of Intrinsically Disordered Regions in the Multidomain Receptor Tyrosine Kinase KIT.International journal of molecular sciences · 2022Article
- TRK xDFG Mutations Trigger a Sensitivity Switch from Type I to II Kinase Inhibitors.Cancer discovery · 2021Article
- Chokepoints in Mechanical Coupling Associated with Allosteric Proteins: The Pyruvate Kinase Example.Biophysical journal · 2019Article
- Coupled regulation by the juxtamembrane and sterile α motif (SAM) linker is a hallmark of ephrin tyrosine kinase evolution.The Journal of biological chemistry · 2018Article
- Survey of solution dynamics in Src kinase reveals allosteric cross talk between the ligand binding and regulatory sites.Nature communications · 2017Article
- Design of Elastic Networks with Evolutionary Optimized Long-Range Communication as Mechanical Models of Allosteric Proteins.Biophysical journal · 2017Article
- The Future of Targeting FLT3 Activation in AML.Current hematologic malignancy reports · 2017Review
- PBxplore: a tool to analyze local protein structure and deformability with Protein Blocks.PeerJ · 2017Article
- Protein Ensembles: How Does Nature Harness Thermodynamic Fluctuations for Life? The Diverse Functional Roles of Conformational Ensembles in the Cell.Chemical reviews · 2016Review
- Trading in cooperativity for specificity to maintain uracil-free DNA.Scientific reports · 2016Article
- Dissecting protein architecture with communication blocks and communicating segment pairs.BMC bioinformatics · 2016Article
- Structural signatures of DRD4 mutants revealed using molecular dynamics simulations: Implications for drug targeting.Journal of molecular modeling · 2016Article
- The activation loop tyrosine 823 is essential for the transforming capacity of the c-Kit oncogenic mutant D816V.Oncogene · 2015Article
- A dynamically coupled allosteric network underlies binding cooperativity in Src kinase.Nature communications · 2015Article
- Decoding Structural Properties of a Partially Unfolded Protein Substrate: En Route to Chaperone Binding.PLoS computational biology · 2015Article
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
A fundamental goal in cellular signaling is to understand allosteric communication, the process by which signals originated at one site in a protein propagate dependably to affect remote functional sites. Here, we describe the allosteric regulation of the receptor tyrosine kinase KIT. Our analysis evidenced that communication routes established between the activation loop (A-loop) and the distant juxtamembrane region (JMR) in the native protein were disrupted by the oncogenic mutation D816V positioned in the A-loop. In silico mutagenesis provided a plausible way of restoring the protein communication detected in the native KIT by introducing a counter-balancing second mutation D792E. The communication patterns observed in the native and mutated KIT correlate perfectly with the structural and dynamical features of these proteins. Particularly, a long-distance effect of the D816V mutation manifested as an important structural re-organization of the JMR in the oncogenic mutant was completely vanished in the double mutant D816V/D792E. This detailed characterization of the allosteric communication in the different forms of KIT, native and mutants, was performed by using a modular network representation composed of communication pathways and independent dynamic segments. Such representation permits to enrich a purely mechanistic interaction-based model of protein communication by the introduction of concerted local atomic fluctuations. This method, validated on KIT receptor, may guide a rational modulation of the physiopathological activities of other receptor tyrosine kinases.
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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.