2017
Conformational disruption of PI3Kδ regulation by immunodeficiency mutations in PIK3CD and PIK3R1
Dornan GL, Siempelkamp BD, Jenkins ML, Vadas O, Lucas CL, Burke JE. Conformational disruption of PI3Kδ regulation by immunodeficiency mutations in PIK3CD and PIK3R1. Proceedings Of The National Academy Of Sciences Of The United States Of America 2017, 114: 1982-1987. PMID: 28167755, PMCID: PMC5338455, DOI: 10.1073/pnas.1617244114.Peer-Reviewed Original ResearchMeSH KeywordsCatalytic DomainCell MembraneClass I Phosphatidylinositol 3-KinasesClass Ia Phosphatidylinositol 3-KinaseEnzyme AssaysEnzyme InhibitorsGain of Function MutationHumansImmunologic Deficiency SyndromesMass SpectrometryModels, MolecularPhenotypePhosphatidylinositol 3-KinasesPrimary Immunodeficiency DiseasesProtein ConformationPurinesQuinazolinonesRandomized Controlled Trials as TopicSequence DeletionConceptsRegulatory subunitCatalytic subunitClass IA catalytic subunitsHydrogen-deuterium exchange mass spectrometryOncogenic mutationsP85 regulatory subunitExchange mass spectrometryClass IA phosphoinositideP85α regulatory subunitPI3K delta syndromeCSH2 domainMolecular basisP110δ catalytic subunitMolecular mechanismsBiochemical assaysSubunits
2016
PI3Kδ and primary immunodeficiencies
Lucas CL, Chandra A, Nejentsev S, Condliffe AM, Okkenhaug K. PI3Kδ and primary immunodeficiencies. Nature Reviews Immunology 2016, 16: 702-714. PMID: 27616589, PMCID: PMC5291318, DOI: 10.1038/nri.2016.93.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCell DifferentiationCellular SenescenceEnzyme ActivationGene Expression RegulationHumansImmune SystemImmunityImmunologic Deficiency SyndromesLymphocyte ActivationLymphocytesMolecular Targeted TherapyMutationPhosphatidylinositol 3-KinasesPhosphoinositide-3 Kinase InhibitorsProtein SubunitsSignal TransductionConceptsPrimary immunodeficiencyT cellsHeterozygous mutationsAntibody replacement therapyStructural lung damageRegulatory T cellsT cell senescencePI3Kδ inhibitor idelalisibRecurrent sinopulmonary infectionsB-cell malignanciesHerpes family virusesMTOR inhibitor rapamycinPI3Kδ syndromeMost patientsLung damageLymphoma trialsReplacement therapyLymphoproliferative diseaseSinopulmonary infectionsAntibody responseP110δ catalytic subunitCell malignanciesB cellsImmune systemPatients