2022
Glioblastoma mutations alter EGFR dimer structure to prevent ligand bias
Hu C, Leche CA, Kiyatkin A, Yu Z, Stayrook SE, Ferguson KM, Lemmon MA. Glioblastoma mutations alter EGFR dimer structure to prevent ligand bias. Nature 2022, 602: 518-522. PMID: 35140400, PMCID: PMC8857055, DOI: 10.1038/s41586-021-04393-3.Peer-Reviewed Original Research
2020
Insulin and epidermal growth factor receptor family members share parallel activation mechanisms
Ferguson KM, Hu C, Lemmon MA. Insulin and epidermal growth factor receptor family members share parallel activation mechanisms. Protein Science 2020, 29: 1331-1344. PMID: 32297376, PMCID: PMC7255510, DOI: 10.1002/pro.3871.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsConceptsReceptor tyrosine kinasesEpidermal growth factor receptorLigand-binding moduleInsulin receptorAutoinhibitory interactionsRecent cryo-electron microscopy structuresCryo-electron microscopy structureFirst receptor tyrosine kinasesRecent cryo-EM structureEGFR activation mechanismsEpidermal growth factor receptor family membersActivated insulin receptorIntramolecular autoinhibitory interactionCryo-EM structureActivation mechanismCysteine-rich domainFibronectin type III domainReceptor family membersEGFR family membersType III domainMicroscopy structureDomain compositionTransmembrane regionGrowth factor receptorLike domain
2018
Molecular basis for necitumumab inhibition of EGFR variants associated with acquired cetuximab resistance.
Bagchi A, Haidar JN, Eastman SW, Vieth M, Topper M, Iacolina MD, Walker JM, Forest A, Shen Y, Novosiadly RD, Ferguson KM. Molecular basis for necitumumab inhibition of EGFR variants associated with acquired cetuximab resistance. Molecular Cancer Therapeutics 2018, 17: molcanther.0575.2017. PMID: 29158469, PMCID: PMC5925748, DOI: 10.1158/1535-7163.mct-17-0575.Peer-Reviewed Original Research
2017
EGFR Ligands Differentially Stabilize Receptor Dimers to Specify Signaling Kinetics
Freed DM, Bessman NJ, Kiyatkin A, Salazar-Cavazos E, Byrne PO, Moore JO, Valley CC, Ferguson KM, Leahy DJ, Lidke DS, Lemmon MA. EGFR Ligands Differentially Stabilize Receptor Dimers to Specify Signaling Kinetics. Cell 2017, 171: 683-695.e18. PMID: 28988771, PMCID: PMC5650921, DOI: 10.1016/j.cell.2017.09.017.Peer-Reviewed Original ResearchConceptsReceptor tyrosine kinasesEpidermal growth factor receptorEGFR ligandsEGFR extracellular regionG protein-coupled receptorsDifferent EGFR ligandsCellular programsDifferent activating ligandsEGFR dimersCell signalingGrowth factor receptorExtracellular regionDimeric conformationEGFR dimerizationNew therapeutic opportunitiesReceptor dimersTyrosine kinaseBreast cancer cellsDimerization strengthActivating ligandsFactor receptorCancer cellsEpigenTherapeutic opportunitiesBiased agonism