ArticleMolecular cell2015
The strength and cooperativity of KIT ectodomain contacts determine normal ligand-dependent stimulation or oncogenic activation in cancer.
Article in Molecular cell, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 32 citations in OpenAlex.
- Nilotinib revisited in GIST: salvage use in patients with severe imatinib toxicity.The oncologist · 2026Article
- Molecular Mechanisms of KIT Receptor Dimerization and Oncogenic Activation Revealed by Multiscale Simulations.Journal of chemical information and modeling · 2026Article
- Endothelial soluble APP/APLP2 promote heart repair through KIT-mediated angiogenesis.Science advances · 2026Article
- Gene Mutations in Gastrointestinal Stromal Tumors: Advances in Treatment and Mechanism Research.Global medical genetics · 2024Review
- Lung-specific MCEMP1 functions as an adaptor for KIT to promote SCF-mediated mast cell proliferation.Nature communications · 2023Article
- Review
- Cryo-EM analyses of KIT and oncogenic mutants reveal structural oncogenic plasticity and a target for therapeutic intervention.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Does Generic Cyclic Kinase Insert Domain of Receptor Tyrosine Kinase KIT Clone Its Native Homologue?International journal of molecular sciences · 2022Article
- State of the structure address on MET receptor activation by HGF.Biochemical Society transactions · 2021Review
- Long-term survival among patients with gastrointestinal stromal tumors diagnosed after another malignancy: a SEER population-based study.World journal of surgical oncology · 2020Article
- Structural Perspectives on Extracellular Recognition and Conformational Changes of Several Type-I Transmembrane Receptors.Frontiers in molecular biosciences · 2020Review
- More than the sum of the parts: Toward full-length receptor tyrosine kinase structures.IUBMB life · 2019Review
- Article
- MET-activating Residues in the B-repeat of the Listeria monocytogenes Invasion Protein InlB.The Journal of biological chemistry · 2016Article
- Distinct cellular properties of oncogenic KIT receptor tyrosine kinase mutants enable alternative courses of cancer cell inhibition.Proceedings of the National Academy of Sciences of the United States of America · 2016Article
Corrections and comments
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
The receptor tyrosine kinase KIT plays an important role in development of germ cells, hematopoietic cells, and interstitial pacemaker cells. Oncogenic KIT mutations play an important "driver" role in gastrointestinal stromal tumors, acute myeloid leukemias, and melanoma, among other cancers. Here we describe the crystal structure of a recurring somatic oncogenic mutation located in the C-terminal Ig-like domain (D5) of the ectodomain, rendering KIT tyrosine kinase activity constitutively activated. The structural analysis, together with biochemical and biophysical experiments and detailed analyses of the activities of a variety of oncogenic KIT mutations, reveals that the strength of homotypic contacts and the cooperativity in the action of D4D5 regions determines whether KIT is normally regulated or constitutively activated in cancers. We propose that cooperative interactions mediated by multiple weak homotypic contacts between receptor molecules are responsible for regulating normal ligand-dependent or oncogenic RTK activation via a "zipper-like" mechanism for receptor activation.
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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.