2023
Mitogen-Activated Protein Kinase Phosphatases: No Longer Undruggable?
Shillingford S, Bennett A. Mitogen-Activated Protein Kinase Phosphatases: No Longer Undruggable? The Annual Review Of Pharmacology And Toxicology 2023, 63: 617-636. PMID: 36662585, PMCID: PMC10127142, DOI: 10.1146/annurev-pharmtox-051921-121923.Peer-Reviewed Original ResearchConceptsMitogen-activated protein kinaseSmall molecule inhibitionProtein kinaseCritical cellular functionsInhibition of PTPsProtein tyrosineCellular functionsProtein substratesPhosphorylated proteinsCell signalingTyrosine residuesAttractive therapeutic targetCellular effectsKinaseNumerous diseasesPTPDiscovery toolTherapeutic developmentTherapeutic targetMetabolic diseasesInhibitionDephosphorylationSignalingMKPProtein
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
1998
Epidermal Growth Factor Receptor and the Adaptor Protein p52Shc Are Specific Substrates of T-Cell Protein Tyrosine Phosphatase
Tiganis T, Bennett A, Ravichandran K, Tonks N. Epidermal Growth Factor Receptor and the Adaptor Protein p52Shc Are Specific Substrates of T-Cell Protein Tyrosine Phosphatase. Molecular And Cellular Biology 1998, 18: 1622-1634. PMID: 9488479, PMCID: PMC108877, DOI: 10.1128/mcb.18.3.1622.Peer-Reviewed Original ResearchMeSH Keywords3T3 CellsAdaptor Proteins, Signal TransducingAdaptor Proteins, Vesicular TransportAnimalsBinding SitesCalcium-Calmodulin-Dependent Protein KinasesCell NucleusCOS CellsCytoplasmEndoplasmic ReticulumEpidermal Growth FactorErbB ReceptorsGRB2 Adaptor ProteinHeLa CellsHumansMiceMitogen-Activated Protein Kinase 1MutagenesisPhosphorylationPhosphotyrosineProtein Tyrosine Phosphatase, Non-Receptor Type 2Protein Tyrosine PhosphatasesProteinsProtein-Tyrosine KinasesShc Signaling Adaptor ProteinsSrc Homology 2 Domain-Containing, Transforming Protein 1Substrate SpecificityTyrosineConceptsT-cell protein tyrosine phosphataseSubstrate-trapping mutantEpidermal growth factor receptorProtein tyrosine phosphatasePTyr proteinsTyrosine phosphataseGrowth factor receptorPTP active siteTyrosine phosphorylated proteinsEGF-induced activationFactor receptorAlternative splicingCellular contextCOS cellsP52ShcNuclear formTC45Endoplasmic reticulumCatalytic acidSpecific substratesProteinMutantsComplex formationSpecific sitesEGF
1993
Activation of the SH2-containing phosphotyrosine phosphatase SH-PTP2 by its binding site, phosphotyrosine 1009, on the human platelet-derived growth factor receptor.
Lechleider R, Sugimoto S, Bennett A, Kashishian A, Cooper J, Shoelson S, Walsh C, Neel B. Activation of the SH2-containing phosphotyrosine phosphatase SH-PTP2 by its binding site, phosphotyrosine 1009, on the human platelet-derived growth factor receptor. Journal Of Biological Chemistry 1993, 268: 21478-21481. PMID: 7691811, DOI: 10.1016/s0021-9258(20)80562-6.Peer-Reviewed Original ResearchConceptsSH-PTP2Platelet-derived growth factor receptorGrowth factor receptorPhosphotyrosyl peptidesFactor receptorSrc homology 2 domainHuman platelet-derived growth factor receptorIntrinsic tyrosine kinase activityPeptide competition assaysTyrosine kinase activitySH2 domainPhosphorylation sitesSignal transductionKinase activityMajor binding siteImmunoprecipitation studiesCompetition assaysTyrosyl residuesBinding sitesEarly eventsProteinLigand additionActivity 5ReceptorsDocking point