Featured Publications
Phosphorylated WNK kinase networks in recoded bacteria recapitulate physiological function
Schiapparelli P, Pirman NL, Mohler K, Miranda-Herrera PA, Zarco N, Kilic O, Miller C, Shah SR, Rogulina S, Hungerford W, Abriola L, Hoyer D, Turk BE, Guerrero-Cázares H, Isaacs FJ, Quiñones-Hinojosa A, Levchenko A, Rinehart J. Phosphorylated WNK kinase networks in recoded bacteria recapitulate physiological function. Cell Reports 2021, 36: 109416. PMID: 34289367, PMCID: PMC8379681, DOI: 10.1016/j.celrep.2021.109416.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid SequenceAnimalsCell Line, TumorCell MovementCell ProliferationEscherichia coliFemaleGlioblastomaHEK293 CellsHumansMaleMice, NudeMiddle AgedPhosphorylationPhosphoserineProtein Serine-Threonine KinasesRecombinant ProteinsSignal TransductionSmall Molecule LibrariesSubstrate SpecificityWNK Lysine-Deficient Protein Kinase 1ConceptsKinase networkAuthentic post-translational modificationsGenetic code expansionPost-translational modificationsProduction of proteinsSmall molecule kinase inhibitorsKinase inhibitorsGenetic codePhosphorylated proteinsCode expansionKinase proteinWNK kinasesPhysiological functionsWNK4 kinaseBiochemical propertiesGlioblastoma cellsKinaseBacterial strainsProteinDistinct sitesPhosphoserineSPAKBacteriaCellular systemsCells
2024
Structural bases for Na+-Cl− cotransporter inhibition by thiazide diuretic drugs and activation by kinases
Zhao Y, Schubert H, Blakely A, Forbush B, Smith M, Rinehart J, Cao E. Structural bases for Na+-Cl− cotransporter inhibition by thiazide diuretic drugs and activation by kinases. Nature Communications 2024, 15: 7006. PMID: 39143061, PMCID: PMC11324901, DOI: 10.1038/s41467-024-51381-y.Peer-Reviewed Original ResearchConceptsNa+-Cl- cotransporterFamilial hyperkalemic hypertensionRenal salt retentionThiazide diuretic drugsNa+-Cl-Cotransporter inhibitionNCC activitySalt reabsorptionDiuretic drugsBlood pressureBalanced electrolyteTreat hypertensionIon translocation pathwayIon translocationThiazideHypertensionSalt retentionOrthosteric siteCo-structureCarboxyl-terminal domainKinase cascadeEdemaChlorthalidoneCotransporterTranslocation
2015
The PINK1-PARKIN Mitochondrial Ubiquitylation Pathway Drives a Program of OPTN/NDP52 Recruitment and TBK1 Activation to Promote Mitophagy
Heo JM, Ordureau A, Paulo JA, Rinehart J, Harper JW. The PINK1-PARKIN Mitochondrial Ubiquitylation Pathway Drives a Program of OPTN/NDP52 Recruitment and TBK1 Activation to Promote Mitophagy. Molecular Cell 2015, 60: 7-20. PMID: 26365381, PMCID: PMC4592482, DOI: 10.1016/j.molcel.2015.08.016.Peer-Reviewed Original ResearchMeSH KeywordsAdaptor Proteins, Signal TransducingCell Cycle ProteinsHeLa CellsHumansMembrane Transport ProteinsMitochondriaMitophagyNuclear ProteinsPhosphorylationProtein KinasesProtein Serine-Threonine KinasesProteomicsSequestosome-1 ProteinTranscription Factor TFIIIAUbiquitinationUbiquitin-Protein LigasesConceptsUbiquitin chainsEfficient mitophagyTBK1 activationPINK1-Parkin pathwayUbiquitylation pathwayAdaptor recruitmentCellular homeostasisMitochondrial retentionTBK1 kinaseDamaged mitochondriaChain bindingMitophagyHeLa cellsMitochondriaPhosphorylationNDP52Positive feedback mechanismPathwayOPTNRecruitmentActivationAmyotrophic lateral sclerosisAssemblyS473Kinase
2013
Mineralocorticoid Receptor Phosphorylation Regulates Ligand Binding and Renal Response to Volume Depletion and Hyperkalemia
Shibata S, Rinehart J, Zhang J, Moeckel G, Castañeda-Bueno M, Stiegler AL, Boggon TJ, Gamba G, Lifton RP. Mineralocorticoid Receptor Phosphorylation Regulates Ligand Binding and Renal Response to Volume Depletion and Hyperkalemia. Cell Metabolism 2013, 18: 660-671. PMID: 24206662, PMCID: PMC3909709, DOI: 10.1016/j.cmet.2013.10.005.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid SequenceAngiotensin IIAnimalsChlorocebus aethiopsCOS CellsCytoplasmElectrolytesHumansHyperkalemiaKidneyLigandsMiceMolecular Sequence DataPhosphoprotein PhosphatasesPhosphorylationPhosphoserinePotassium, DietaryProtein Serine-Threonine KinasesProtein TransportRatsReceptors, MineralocorticoidSignal TransductionTranscriptional ActivationConceptsVolume depletionMineralocorticoid receptorAldosterone-dependent increaseHormone receptor activityNuclear hormone receptor activityMR activationRenal responseDistinct adaptive responsesAngiotensin IIDistal nephronCl reabsorptionHyperkalemiaMR ligand-binding domainReceptor activityApical proton pumpPlasma volumeReceptor bindingHomeostatic responseNuclear receptorsReceptor phosphorylation