2022
Autoinhibition of the GEF activity of cytoskeletal regulatory protein Trio is disrupted in neurodevelopmental disorder-related genetic variants
Bircher JE, Corcoran EE, Lam TT, Trnka MJ, Koleske AJ. Autoinhibition of the GEF activity of cytoskeletal regulatory protein Trio is disrupted in neurodevelopmental disorder-related genetic variants. Journal Of Biological Chemistry 2022, 298: 102361. PMID: 35963430, PMCID: PMC9467883, DOI: 10.1016/j.jbc.2022.102361.Peer-Reviewed Original ResearchConceptsSpectrin repeatsGEF1 domainPleckstrin homology regionExchange factor domainKey regulatory mechanismCytoskeletal regulatory proteinsSmall GTPase Rac1Autoinhibitory constraintsAccessory domainsNeurodevelopmental disordersGEF activityMultiple neurodevelopmental disordersKinase domainHomology regionProtein TrioGTPase Rac1Regulatory proteinsRegulatory mechanismsFactor domainSRS-6Genetic variantsGef1Disease variantsEnzymatic activityBio-Layer Interferometry
2021
What is the role of synaptic protein TRIO's spectrin repeats?
Corcoran E, Bircher J, Koleske A. What is the role of synaptic protein TRIO's spectrin repeats? The FASEB Journal 2021, 35 DOI: 10.1096/fasebj.2021.35.s1.01837.Peer-Reviewed Original ResearchSpectrin repeatsProper neuronal developmentSpectrin repeat domainRare damaging variantsDisease-associated mutationsAccessory domainsCatalytic domainRepeat domainRegulatory proteinsRepeat functionDe novo missense mutationsSignaling mechanismDamaging mutationsNeuronal developmentDamaging variantsDisease mutationsBiochemical eventsNovo missense mutationNeurodevelopmental disordersMissense mutationsSpectrinRepeatsMutationsDomainTherapeutic strategies
2018
Noonan Syndrome-Associated SHP2 Dephosphorylates GluN2B to Regulate NMDA Receptor Function
Levy AD, Xiao X, Shaw JE, Devi S, Katrancha SM, Bennett AM, Greer CA, Howe JR, Machida K, Koleske AJ. Noonan Syndrome-Associated SHP2 Dephosphorylates GluN2B to Regulate NMDA Receptor Function. Cell Reports 2018, 24: 1523-1535. PMID: 30089263, PMCID: PMC6234505, DOI: 10.1016/j.celrep.2018.07.006.Peer-Reviewed Original ResearchConceptsTyrosine phosphatase SHP2Noonan syndromePhosphatase SHP2Regulatory proteinsSHP2Recombinant GluN1Nck2Receptor functionNMDA receptor functionNMDAR functionGluN2B functionMutationsNMDAR dysfunctionNeuron functionNS miceGluN1ProteinAllelesNMDA receptorsDiheteromersReceptor kineticsReduced contributionsFunctionHyperactivationMice
2008
The c-Abl tyrosine kinase regulates actin remodeling at the immune synapse
Huang Y, Comiskey EO, Dupree RS, Li S, Koleske AJ, Burkhardt JK. The c-Abl tyrosine kinase regulates actin remodeling at the immune synapse. Blood 2008, 112: 111-119. PMID: 18305217, PMCID: PMC2435682, DOI: 10.1182/blood-2007-10-118232.Peer-Reviewed Original ResearchMeSH KeywordsActinsAdaptor Proteins, Signal TransducingAnimalsCells, CulturedHumansInterleukin-2Jurkat CellsLymphocyte ActivationMiceMice, KnockoutPhosphorylationProtein BindingProteinsProto-Oncogene Proteins c-ablPseudopodiaReceptors, Antigen, T-CellSignal TransductionT-LymphocytesTranscription, GeneticWiskott-Aldrich Syndrome Protein FamilyConceptsC-AblImmune synapseActin responseC-Abl nonreceptor tyrosine kinaseT cell activationTyrosine kinaseC-Abl tyrosine kinaseC-Abl bindsActin regulatory proteinsNonreceptor tyrosine kinaseChemokine-induced T cell migrationT cell receptor engagementSH2 domainActin dynamicsActin reorganizationTyrosine phosphorylationRegulatory proteinsActin polymerizationDownstream eventsNormal localizationConditional knockout miceCoordinate actionReceptor engagementKinaseLamellipodial spreading
2004
How do Abl family kinases regulate cell shape and movement?
Hernández SE, Krishnaswami M, Miller AL, Koleske AJ. How do Abl family kinases regulate cell shape and movement? Trends In Cell Biology 2004, 14: 36-44. PMID: 14729179, DOI: 10.1016/j.tcb.2003.11.003.Peer-Reviewed Original ResearchConceptsAbl family kinasesFamily kinasesAdhesion receptorsC-terminal halfCytoskeletal regulatory proteinsNonreceptor tyrosine kinaseCell morphogenesisCytoskeletal dynamicsRecent biochemicalCytoskeletal rearrangementsCytoskeletal structuresCytoskeletal componentsRegulatory proteinsCell shapeGenetic analysisTyrosine kinaseKinaseCell surfaceARG proteinRelay signalsProteinLeukemia cellsDrosophilaCrystallographic analysisMorphogenesis
1995
A kinase–cyclin pair in the RNA polymerase II holoenzyme
Liao S, Zhang J, Jeffery D, Koleske A, Thompson C, Chao D, Viljoen M, van Vuuren H, Young R. A kinase–cyclin pair in the RNA polymerase II holoenzyme. Nature 1995, 374: 193-196. PMID: 7877695, DOI: 10.1038/374193a0.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid SequenceCyclin-Dependent Kinase 8Cyclin-Dependent KinasesCyclinsFungal ProteinsMolecular Sequence DataMutationProtein Serine-Threonine KinasesRNA Polymerase IISaccharomyces cerevisiaeSaccharomyces cerevisiae ProteinsSequence Homology, Amino AcidTranscription FactorsTranscription, GeneticConceptsRNA polymerase II holoenzymeSRB proteinsKinase functionRNA polymerase II carboxy-terminal domainCyclin-like proteinGeneral transcription factorsRNA polymerase IISuppressors of mutationsNormal transcriptional responseCarboxy-terminal domainPolymerase IITranscriptional regulatorsTranscriptional responseGalactose inductionTranscription factorsRegulatory proteinsTranscription systemHoloenzymeRegulatory roleKinaseProteinBiochemical evidenceGenesVivoSrb11
1994
An RNA polymerase II holoenzyme responsive to activators
Koleske A, Young R. An RNA polymerase II holoenzyme responsive to activators. Nature 1994, 368: 466-469. PMID: 8133894, DOI: 10.1038/368466a0.Peer-Reviewed Original ResearchConceptsRNA polymerase IIGeneral transcription factorsRNA polymerase II holoenzymePolymerase IITranscription factorsPromoter DNAMulti-component complexesGAL4-VP16Initiation factorsRegulatory proteinsHoloenzymeProteinDNAOrdered fashionCerevisiaeTranscriptionVivoPromoterActivatorAssemblyEquimolar amountsComplexes