Featured Publications
A flexible codon in genomically recoded Escherichia coli permits programmable protein phosphorylation
Pirman NL, Barber KW, Aerni HR, Ma NJ, Haimovich AD, Rogulina S, Isaacs FJ, Rinehart J. A flexible codon in genomically recoded Escherichia coli permits programmable protein phosphorylation. Nature Communications 2015, 6: 8130. PMID: 26350500, PMCID: PMC4566969, DOI: 10.1038/ncomms9130.Peer-Reviewed Original ResearchConceptsProtein phosphorylationProtein phosphorylation eventsFull-length proteinNon-phosphorylated formPhosphoserine-containing proteinsPhosphorylation eventsMEK1 kinaseUAG codonKinase activityRecombinant DNADNA templateEscherichia coliE. coliCodonPhosphorylationFunctional informationSerineProteinColiBiochemical investigationsPhosphoproteomeInefficient productionKinasePhosphoserineDNA
2023
System‐wide optimization of an orthogonal translation system with enhanced biological tolerance
Mohler K, Moen J, Rogulina S, Rinehart J. System‐wide optimization of an orthogonal translation system with enhanced biological tolerance. Molecular Systems Biology 2023, 19: msb202110591. PMID: 37477096, PMCID: PMC10407733, DOI: 10.15252/msb.202110591.Peer-Reviewed Original ResearchConceptsOrthogonal translation systemHost interactionsNon-standard amino acidsPost-translational modificationsSystems-level biologyStress response activationTranslation systemSynthetic biological systemsCellular physiologyProtein phosphorylationOTS performanceHost physiologyCellular environmentAmino acidsCellular mechanismsDeleterious interactionsResponse activationBiological systemsPhysiologyOTS developmentUnparalleled accessPhosphorylationHost toxicityBiologyInteraction
2022
Enhanced access to the human phosphoproteome with genetically encoded phosphothreonine
Moen J, Mohler K, Rogulina S, Shi X, Shen H, Rinehart J. Enhanced access to the human phosphoproteome with genetically encoded phosphothreonine. Nature Communications 2022, 13: 7226. PMID: 36433969, PMCID: PMC9700786, DOI: 10.1038/s41467-022-34980-5.Peer-Reviewed Original ResearchConceptsUbiquitous post-translational modificationCo-translational insertionKinase activation mechanismProtein interaction platformOrthogonal translation systemProtein-protein interactionsPost-translational modificationsPhospho-amino acidsAminoacyl-tRNA synthetaseHuman phosphoproteomePhosphorylation eventsTRNA pairsFunctional assignmentCellular processesProtein phosphorylationUpstream kinasePhysiological functionsActivation mechanismTranslation systemKinasePhosphorylationInteraction platformPhosphoproteomePhosphothreoninePhospho
2019
Distinct Hepatic PKA and CDK Signaling Pathways Control Activity-Independent Pyruvate Kinase Phosphorylation and Hepatic Glucose Production
Gassaway BM, Cardone RL, Padyana AK, Petersen MC, Judd ET, Hayes S, Tong S, Barber KW, Apostolidi M, Abulizi A, Sheetz JB, Kshitiz, Aerni HR, Gross S, Kung C, Samuel VT, Shulman GI, Kibbey RG, Rinehart J. Distinct Hepatic PKA and CDK Signaling Pathways Control Activity-Independent Pyruvate Kinase Phosphorylation and Hepatic Glucose Production. Cell Reports 2019, 29: 3394-3404.e9. PMID: 31825824, PMCID: PMC6951436, DOI: 10.1016/j.celrep.2019.11.009.Peer-Reviewed Original ResearchConceptsCyclin-dependent kinasesMetabolic control pointPhosphorylation sitesNuclear retentionCDK activityPKL activityDays high-fat dietKinase phosphorylationImportant enzymePyruvate kinaseHigh-fat dietS113KinaseEnzyme kineticsPhosphorylationAdditional control pointsRegulationGlucose productionHepatic glucose productionInsulin resistanceGlycolysisEnzymePKAPathwayActivity
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 sclerosisAssemblyS473KinaseRobust production of recombinant phosphoproteins using cell-free protein synthesis
Oza JP, Aerni HR, Pirman NL, Barber KW, ter Haar CM, Rogulina S, Amrofell MB, Isaacs FJ, Rinehart J, Jewett MC. Robust production of recombinant phosphoproteins using cell-free protein synthesis. Nature Communications 2015, 6: 8168. PMID: 26350765, PMCID: PMC4566161, DOI: 10.1038/ncomms9168.Peer-Reviewed Original ResearchConceptsMEK1 activityMultiple phosphorylated residuesCo-translational incorporationSite-specific protein phosphorylationCell-free protein synthesis platformHigh-throughput technology platformsCell-free protein synthesisSite-specific phosphorylationStructure-function relationshipsRecombinant phosphoproteinsPhosphorylation eventsMEK1 kinasePhosphorylated residuesProtein phosphorylationProtein synthesisEscherichia coliPhosphoproteinRobust productionSynthesis platformStructural consequencesDirect expressionPhosphorylationTechnology platformKinasePhosphoserine
2013
Src‐family protein tyrosine kinase (SFK) stimulates KCNJ10 K channels in the basolateral membrane of distal convoluted tubules (DCT).
Wang W, Zhang C, Lin D, Yue P, Wang L, Rinehart J. Src‐family protein tyrosine kinase (SFK) stimulates KCNJ10 K channels in the basolateral membrane of distal convoluted tubules (DCT). The FASEB Journal 2013, 27: 911.1-911.1. DOI: 10.1096/fasebj.27.1_supplement.911.1.Peer-Reviewed Original ResearchSrc family protein tyrosine kinasesPhosphorylation sitesWhole-cell K currentsTyrosine phosphorylationTyr-8Tyr-9Tyrosine phosphorylation sitesProtein tyrosine kinasesTyrosine phosphorylated proteinsBasolateral K channelsPhosphorylated proteinsBasolateral Cl(-) exitSFK activityHigh K dietTyrosine kinaseK channelsPhysiological roleHEK293 cellsCl exitHEK cellsDCT1Patch-clamp experimentsBasolateral membraneKCNJ10PhosphorylationSrc‐family tyrosine kinase (SFK) phosphorylates With‐No‐ Lysine Kinase4 (WNK4) and modulates the inhibitory effect of WNK4 on ROMK channels.
Lin D, Yue P, Yarborough O, Lifton R, Rinehart J, Wang W. Src‐family tyrosine kinase (SFK) phosphorylates With‐No‐ Lysine Kinase4 (WNK4) and modulates the inhibitory effect of WNK4 on ROMK channels. The FASEB Journal 2013, 27: 911.2-911.2. DOI: 10.1096/fasebj.27.1_supplement.911.2.Peer-Reviewed Original Research
2009
Sites of Regulated Phosphorylation that Control K-Cl Cotransporter Activity
Rinehart J, Maksimova Y, Tanis J, Stone K, Hodson C, Zhang J, Risinger M, Pan W, Wu D, Colangelo C, Forbush B, Joiner C, Gulcicek E, Gallagher P, Lifton R. Sites of Regulated Phosphorylation that Control K-Cl Cotransporter Activity. Journal Of End-to-End-testing 2009, 138: 525-536. DOI: 10.1016/s9999-9994(09)20441-7.Peer-Reviewed Original ResearchIntrinsic transport activityK-Cl cotransporterTransport activityCell volume regulationRegulated phosphorylationRNA interferenceAlanine substitutionsCultured cellsHomologous sitesKCC activityWNK1 expressionNeonatal mouse brainVolume regulationNeuronal functionHypotonic conditionsActive cotransportPhosphorylationIntracellular chloride concentrationCotransporter activityKCC3Human red blood cellsKCC2 activationFundamental roleMouse brainRegulationSites of Regulated Phosphorylation that Control K-Cl Cotransporter Activity
Rinehart J, Maksimova YD, Tanis JE, Stone KL, Hodson CA, Zhang J, Risinger M, Pan W, Wu D, Colangelo CM, Forbush B, Joiner CH, Gulcicek EE, Gallagher PG, Lifton RP. Sites of Regulated Phosphorylation that Control K-Cl Cotransporter Activity. Cell 2009, 138: 525-536. PMID: 19665974, PMCID: PMC2811214, DOI: 10.1016/j.cell.2009.05.031.Peer-Reviewed Original ResearchConceptsIntrinsic transport activityK-Cl cotransporterTransport activityCell volume regulationRegulated phosphorylationRNA interferenceAlanine substitutionsCultured cellsHomologous sitesKCC activityCl exitWNK1 expressionNeonatal mouse brainVolume regulationNeuronal functionHypotonic conditionsActive cotransportPhosphorylationIntracellular chloride concentrationCotransporter activityKCC3Human red blood cellsKCC2 activationFundamental roleMouse brain