2014
The Strength and Cooperativity of KIT Ectodomain Contacts Determine Normal Ligand-Dependent Stimulation or Oncogenic Activation in Cancer
Reshetnyak AV, Opatowsky Y, Boggon TJ, Folta-Stogniew E, Tome F, Lax I, Schlessinger J. The Strength and Cooperativity of KIT Ectodomain Contacts Determine Normal Ligand-Dependent Stimulation or Oncogenic Activation in Cancer. Molecular Cell 2014, 57: 191-201. PMID: 25544564, PMCID: PMC4764128, DOI: 10.1016/j.molcel.2014.11.021.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBaculoviridaeBinding SitesCrystallography, X-RayEnzyme ActivationHumansLigandsMiceModels, MolecularMutationNeoplasmsNIH 3T3 CellsProtein BindingProtein FoldingProtein Interaction Domains and MotifsProtein MultimerizationProtein Structure, SecondaryProto-Oncogene Proteins c-kitRecombinant ProteinsSf9 CellsSpodopteraConceptsOncogenic KIT mutationsKIT mutationsGastrointestinal stromal tumorsAcute myeloid leukemiaKIT tyrosine kinase activitySomatic oncogenic mutationsInterstitial pacemaker cellsLigand-dependent stimulationReceptor tyrosine kinase KITStromal tumorsTyrosine kinase KITMyeloid leukemiaReceptor activationPacemaker cellsTyrosine kinase activityCancerKinase KITOncogenic mutationsHematopoietic cellsGerm cellsOncogenic activationActivationCellsReceptor moleculesMutations
2006
Attenuation of signaling pathways stimulated by pathologically activated FGF-receptor 2 mutants prevents craniosynostosis
Eswarakumar VP, Özcan F, Lew ED, Bae JH, Tomé F, Booth CJ, Adams DJ, Lax I, Schlessinger J. Attenuation of signaling pathways stimulated by pathologically activated FGF-receptor 2 mutants prevents craniosynostosis. Proceedings Of The National Academy Of Sciences Of The United States Of America 2006, 103: 18603-18608. PMID: 17132737, PMCID: PMC1693709, DOI: 10.1073/pnas.0609157103.Peer-Reviewed Original ResearchConceptsFGF receptorsDocking protein FRS2alphaCommon craniofacial abnormalitySelective uncouplingPremature fusionSkull developmentFunction mutationsDominant mutationsNormal skull developmentMurine model systemMutationsSevere bone disordersModel systemFGFR2cCraniofacial abnormalitiesCalvaria organ culturesPathwayOrgan cultureFRS2alphaSkull vaultMutantsPharmacological approachesFusionFGFRUncoupling