2015
Heparin is an activating ligand of the orphan receptor tyrosine kinase ALK
Murray PB, Lax I, Reshetnyak A, Ligon GF, Lillquist JS, Natoli EJ, Shi X, Folta-Stogniew E, Gunel M, Alvarado D, Schlessinger J. Heparin is an activating ligand of the orphan receptor tyrosine kinase ALK. Science Signaling 2015, 8: ra6. PMID: 25605972, DOI: 10.1126/scisignal.2005916.Peer-Reviewed Original ResearchConceptsAnaplastic lymphoma kinaseReceptor tyrosine kinasesActivation of RTKsCultured neuroblastoma cellsReceptor tyrosine kinase anaplastic lymphoma kinaseActivation of ALKStroma contributesLung adenocarcinomaLymphoma kinaseNervous systemExtracellular domainDrug resistanceNeuroblastoma cellsAberrant activationALK activityHeparinCancerPotential mechanismsGenetic amplificationActivationTyrosine kinaseAdenocarcinomaNeuroblastomaTherapyProgression
2013
Structural basis for KIT receptor tyrosine kinase inhibition by antibodies targeting the D4 membrane-proximal region
Reshetnyak AV, Nelson B, Shi X, Boggon TJ, Pavlenco A, Mandel-Bausch EM, Tome F, Suzuki Y, Sidhu SS, Lax I, Schlessinger J. Structural basis for KIT receptor tyrosine kinase inhibition by antibodies targeting the D4 membrane-proximal region. Proceedings Of The National Academy Of Sciences Of The United States Of America 2013, 110: 17832-17837. PMID: 24127596, PMCID: PMC3816449, DOI: 10.1073/pnas.1317118110.Peer-Reviewed Original ResearchConceptsKIT antibodyReceptor tyrosine kinase inhibitionGastrointestinal stromal tumorsAcute myeloid leukemiaDurable disease controlTyrosine kinase inhibitorsTyrosine kinase inhibitionSomatic oncogenic mutationsUnique therapeutic approachClinical progressionStromal tumorsMyeloid leukemiaTherapeutic approachesDramatic responseTreatment of KITDrug resistanceDisease controlIsolated antibodyKIT inhibitionKinase inhibitorsAntibodiesCancerCell proliferationOncogenic mutationsKinase inhibition