ArticlePLoS computational biology2014
Hotspot mutations in KIT receptor differentially modulate its allosterically coupled conformational dynamics: impact on activation and drug sensitivity.
Article in PLoS computational biology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 32 citations in OpenAlex.
- Novel somatic Missense Mutations in Exon 11 of the KIT Gene are Detected in Melanoma.Asian Pacific journal of cancer prevention : APJCP · 2023Article
- Molecular Dynamics and Machine Learning Give Insights on the Flexibility-Activity Relationships in Tyrosine Kinome.Journal of chemical information and modeling · 2023Article
- c-Kit Receptors as a Therapeutic Target in Cancer: Current Insights.OncoTargets and therapy · 2023Review
- Role and significance of c-KIT receptor tyrosine kinase in cancer: A review.Bosnian journal of basic medical sciences · 2022Review
- Inhibitory effects of isoliquiritin on an atopic dermatitis model through the CD177/JAK2/STAT pathwayAnnals of translational medicine · 2022Article
- The Inherent Coupling of Intrinsically Disordered Regions in the Multidomain Receptor Tyrosine Kinase KIT.International journal of molecular sciences · 2022Article
- Clinical Impact of Inherited and Acquired Genetic Variants in Mastocytosis.International journal of molecular sciences · 2021Review
- "Infostery" analysis of short molecular dynamics simulations identifies highly sensitive residues and predicts deleterious mutations.Scientific reports · 2018Article
- Dissecting protein architecture with communication blocks and communicating segment pairs.BMC bioinformatics · 2016Article
- Insight on Mutation-Induced Resistance from Molecular Dynamics Simulations of the Native and Mutated CSF-1R and KIT.PloS one · 2016Article
- Genome-Wide Transcriptional and Post-transcriptional Regulation of Innate Immune and Defense Responses of Bovine Mammary Gland toFrontiers in cellular and infection microbiology · 2016Article
- Structural signatures of DRD4 mutants revealed using molecular dynamics simulations: Implications for drug targeting.Journal of molecular modeling · 2016Article
- Article
- 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
7 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Receptor tyrosine kinase KIT controls many signal transduction pathways and represents a typical allosterically regulated protein. The mutation-induced deregulation of KIT activity impairs cellular physiological functions and causes serious human diseases. The impact of hotspots mutations (D816H/Y/N/V and V560G/D) localized in crucial regulatory segments, the juxtamembrane region (JMR) and the activation (A-) loop, on KIT internal dynamics was systematically studied by molecular dynamics simulations. The mutational outcomes predicted in silico were correlated with in vitro and in vivo activation rates and drug sensitivities of KIT mutants. The allosteric regulation of KIT in the native and mutated forms is described in terms of communication between the two remote segments, JMR and A-loop. A strong correlation between the communication profile and the structural and dynamical features of KIT in the native and mutated forms was established. Our results provide new insight on the determinants of receptor KIT constitutive activation by mutations and resistance of KIT mutants to inhibitors. Depiction of an intra-molecular component of the communication network constitutes a first step towards an integrated description of vast communication pathways established by KIT in physiopathological contexts.
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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.