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
2007
Structural basis for reduced FGFR2 activity in LADD syndrome: Implications for FGFR autoinhibition and activation
Lew ED, Bae JH, Rohmann E, Wollnik B, Schlessinger J. Structural basis for reduced FGFR2 activity in LADD syndrome: Implications for FGFR autoinhibition and activation. Proceedings Of The National Academy Of Sciences Of The United States Of America 2007, 104: 19802-19807. PMID: 18056630, PMCID: PMC2148379, DOI: 10.1073/pnas.0709905104.Peer-Reviewed Original ResearchMeSH KeywordsAbnormalities, MultipleAdenosine TriphosphateAlanineCrystallography, X-RayHumansModels, MolecularMutationPhosphorylationProtein BindingProtein Structure, TertiaryReceptor, Fibroblast Growth Factor, Type 1Receptor, Fibroblast Growth Factor, Type 2Structural Homology, ProteinSubstrate SpecificitySyndromeConceptsFibroblast growth factor receptor 2Tyrosine kinase activityKinase activityStatic crystallographic snapshotsKinase hinge regionSevere skeletal disorderTyrosine kinase domainAutophosphorylation kineticsFGFR2 kinaseFGFR1 kinaseKinase domainKey residuesStructural basisMutation altersFGFR2 activityConformational dynamicsCrystallographic snapshotsStringent modeCatalytic pocketFGF receptorsFunction mutationsKinaseMultiple gainsMissense mutationsAutoinhibitionStructural Basis for Activation of the Receptor Tyrosine Kinase KIT by Stem Cell Factor
Yuzawa S, Opatowsky Y, Zhang Z, Mandiyan V, Lax I, Schlessinger J. Structural Basis for Activation of the Receptor Tyrosine Kinase KIT by Stem Cell Factor. Cell 2007, 130: 323-334. PMID: 17662946, DOI: 10.1016/j.cell.2007.05.055.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid SequenceBinding SitesCrystallography, X-RayDimerizationDiseaseEnzyme ActivationHumansLigandsModels, MolecularMolecular Sequence DataMutationProtein BindingProtein Structure, SecondaryProtein Structure, TertiaryProto-Oncogene Proteins c-kitStem Cell FactorStructure-Activity RelationshipConceptsStem cell factorReceptor dimerizationLigand-induced receptor dimerizationCell factorMultiple cellular responsesTyrosine kinase activationReceptor tyrosine kinase KITKIT dimerizationTyrosine kinase KITDomain D4Structural basisCritical residuesKinase activationSCF stimulationCellular responsesConformational changesOncogenic mutationsCultured cellsAmino acidsPoint mutationsKIT activationEntire ectodomainKinase KITKey hallmarksSole role