2023
Mutation of key signaling regulators of cerebrovascular development in vein of Galen malformations
Zhao S, Mekbib K, van der Ent M, Allington G, Prendergast A, Chau J, Smith H, Shohfi J, Ocken J, Duran D, Furey C, Hao L, Duy P, Reeves B, Zhang J, Nelson-Williams C, Chen D, Li B, Nottoli T, Bai S, Rolle M, Zeng X, Dong W, Fu P, Wang Y, Mane S, Piwowarczyk P, Fehnel K, See A, Iskandar B, Aagaard-Kienitz B, Moyer Q, Dennis E, Kiziltug E, Kundishora A, DeSpenza T, Greenberg A, Kidanemariam S, Hale A, Johnston J, Jackson E, Storm P, Lang S, Butler W, Carter B, Chapman P, Stapleton C, Patel A, Rodesch G, Smajda S, Berenstein A, Barak T, Erson-Omay E, Zhao H, Moreno-De-Luca A, Proctor M, Smith E, Orbach D, Alper S, Nicoli S, Boggon T, Lifton R, Gunel M, King P, Jin S, Kahle K. Mutation of key signaling regulators of cerebrovascular development in vein of Galen malformations. Nature Communications 2023, 14: 7452. PMID: 37978175, PMCID: PMC10656524, DOI: 10.1038/s41467-023-43062-z.Peer-Reviewed Original ResearchConceptsEphrin receptor B4Galen malformationBrain arteriovenous malformationsP120 RasGAPTransmitted variantsArteriovenous malformationsDe novo variantsSingle-cell transcriptomesSignificant burdenCerebrovascular developmentIntegrative genomic analysisEndothelial cellsVenous networkAdditional probandsMalformationsNovo variantsMissense variantsGenomic analysisDevelopmental angiogenesisVascular developmentDamaging variantsVeinRasGAPIntegrated analysisPatientsDiverse p120RasGAP interactions with doubly phosphorylated partners EphB4, p190RhoGAP, and Dok1
Vish K, Stiegler A, Boggon T. Diverse p120RasGAP interactions with doubly phosphorylated partners EphB4, p190RhoGAP, and Dok1. Journal Of Biological Chemistry 2023, 299: 105098. PMID: 37507023, PMCID: PMC10470053, DOI: 10.1016/j.jbc.2023.105098.Peer-Reviewed Original ResearchConceptsSH2 domainSpatial-temporal regulationDual SH2 domainsProper vascular developmentKey binding partnerProtein familySH2 interactionsBinding partnerHuman proteinsDistinct binding interactionsWeakened affinityVascular developmentRasGAPConformational differencesP190RhoGAPSmall-angle X-ray scatteringBindingBinding interactionsAffinity measurementsEphB4DomainGTPaseDok1X-ray scatteringProtein
2022
Tandem engagement of phosphotyrosines by the dual SH2 domains of p120RasGAP
Stiegler A, Vish K, Boggon T. Tandem engagement of phosphotyrosines by the dual SH2 domains of p120RasGAP. Structure 2022, 30: 1603-1614.e5. PMID: 36417908, PMCID: PMC9722645, DOI: 10.1016/j.str.2022.10.009.Peer-Reviewed Original ResearchMeSH KeywordsGTPase-Activating ProteinsP120 GTPase Activating ProteinPhosphotyrosineSrc Homology DomainsTyrosineConceptsGTPase-activating proteinsSH2 domainSH2-SH3Src homology 2 domainDual SH2 domainsPhosphotyrosine residuesSH3 domainRho GTPasesPhosphotyrosine recognitionTarget proteinsSynergistic bindingPhosphotyrosineP120RasGAPConformational flexibilityProteinSelectivity mechanismAffinity measurementsDomainGTPasesClose proximityCassetteCrystal structureResiduesCompact arrangementBinding