2016
MK-2206 sensitizes BRCA-deficient epithelial ovarian adenocarcinoma to cisplatin and olaparib
Whicker ME, Lin ZP, Hanna R, Sartorelli AC, Ratner ES. MK-2206 sensitizes BRCA-deficient epithelial ovarian adenocarcinoma to cisplatin and olaparib. BMC Cancer 2016, 16: 550. PMID: 27465688, PMCID: PMC4964088, DOI: 10.1186/s12885-016-2598-1.Peer-Reviewed Original ResearchMeSH KeywordsBRCA1 ProteinCarcinoma, Ovarian EpithelialCell Line, TumorCell SurvivalCisplatinDrug SynergismFemaleGene Expression Regulation, NeoplasticHeterocyclic Compounds, 3-RingHumansMutationNeoplasms, Glandular and EpithelialOvarian NeoplasmsPhosphorylationPhthalazinesPiperazinesProto-Oncogene Proteins c-aktConceptsEpithelial ovarian cancerOlaparib therapyOvarian adenocarcinomaPhase II trialGreater clinical responseSerous ovarian adenocarcinomaPhospho-AKT activityAgent-induced DNA damageAkt activityEpithelial ovarian adenocarcinomaII trialPeritoneal cancerClinical responseInhibition of AktPatient populationStrong synergismFallopian tubeOvarian cancerHomologous recombination repair pathwaySame patientChemosensitization agentsClinical investigationChemoresistant cellsPlatinum resistanceBRCA-deficient cellsSerine 302 Phosphorylation of Mouse Insulin Receptor Substrate 1 (IRS1) Is Dispensable for Normal Insulin Signaling and Feedback Regulation by Hepatic S6 Kinase*
Copps K, Hançer N, Qiu W, White M. Serine 302 Phosphorylation of Mouse Insulin Receptor Substrate 1 (IRS1) Is Dispensable for Normal Insulin Signaling and Feedback Regulation by Hepatic S6 Kinase*. Journal Of Biological Chemistry 2016, 291: 8602-8617. PMID: 26846849, PMCID: PMC4861431, DOI: 10.1074/jbc.m116.714915.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid SubstitutionAnimalsCHO CellsCricetinaeCricetulusGene DeletionGlucose IntoleranceInsulinInsulin Receptor Substrate ProteinsLiverMechanistic Target of Rapamycin Complex 1MiceMice, TransgenicMultiprotein ComplexesMutation, MissensePhosphatidylinositol 3-KinasesPhosphorylationProto-Oncogene Proteins c-aktRibosomal Protein S6 KinasesSerineSignal TransductionTOR Serine-Threonine KinasesTuberous Sclerosis Complex 1 ProteinTumor Suppressor ProteinsConceptsInsulin receptor substrate-1Receptor substrate-1PI3K associationS6 kinaseSubstrate-1Insulin-stimulated Akt activityAkt phosphorylationK associationRapamycin complex 1S6K signalingInsulin-stimulated IRS1 tyrosine phosphorylationSer-302IRS1 tyrosine phosphorylationMTORC1 inhibitor rapamycinRibosomal S6 proteinTsc1 deletionFeedback phosphorylationIntracellular amino acidsInsulin sensitivityTyrosine phosphorylationAlanine mutationsS6 proteinS6KAkt activityInsulin signaling
2011
Compensatory Signaling From ROR1 and the Pre-B Cell Receptor Promote Survival of t(1;19) Acute Lymphoblastic Leukemia
Bicocca V, Chang B, Muschen M, Druker B, Tyner J. Compensatory Signaling From ROR1 and the Pre-B Cell Receptor Promote Survival of t(1;19) Acute Lymphoblastic Leukemia. Blood 2011, 118: 2466. DOI: 10.1182/blood.v118.21.2466.2466.Peer-Reviewed Original ResearchTyrosine kinaseAcute lymphoblastic leukemiaAkt activityPre-B cell receptor signalingCell linesLeukemogenic tyrosine kinasesProtein target identificationKinase inhibitor screenImmunoblot analysisCell receptor signalingCell viabilityKinase inhibitor screeningClinical trial contractsReceptor tyrosine kinasesTyrosine kinase activityPhospho-protein arraysSmall molecule inhibitorsROR1 knockdownSiRNA screeningAkt regulationLymphoblastic leukemiaDasatinib treatmentKinase domainPatient costsLeukemia patientsmTOR Complex 2 Targets Akt for Proteasomal Degradation via Phosphorylation at the Hydrophobic Motif*
Wu YT, Ouyang W, Lazorchak AS, Liu D, Shen HM, Su B. mTOR Complex 2 Targets Akt for Proteasomal Degradation via Phosphorylation at the Hydrophobic Motif*. Journal Of Biological Chemistry 2011, 286: 14190-14198. PMID: 21321111, PMCID: PMC3077620, DOI: 10.1074/jbc.m111.219923.Peer-Reviewed Original ResearchConceptsAkt Ser-473 phosphorylationSer-473 phosphorylationAkt activationMotif phosphorylationHydrophobic motifProteasomal degradationHydrophobic motif phosphorylationLys-48-linked polyubiquitinationPhosphorylation-dependent ubiquitinationRapid proteasomal degradationProtein kinase AktRapamycin complex 2Protein life cycleDiverse human diseasesFull Akt activationActivity of AktNegative feedback regulationCellular stimuliKinase AktDependent phosphorylationProtein degradationTarget AktAkt activityHuman diseasesAkt protein
2007
Extrinsic pathway- and cathepsin-dependent induction of mitochondrial dysfunction are essential for synergistic flavopiridol and vorinostat lethality in breast cancer cells
Mitchell C, Park MA, Zhang G, Yacoub A, Curiel DT, Fisher PB, Roberts JD, Grant S, Dent P. Extrinsic pathway- and cathepsin-dependent induction of mitochondrial dysfunction are essential for synergistic flavopiridol and vorinostat lethality in breast cancer cells. Molecular Cancer Therapeutics 2007, 6: 3101-3112. PMID: 18065490, DOI: 10.1158/1535-7163.mct-07-0561.Peer-Reviewed Original ResearchConceptsBcl-xLC-FLIPBreast cancer cellsMitogen-activated protein/ERK kinase 1X-chromosome-linked inhibitorCancer cellsExtracellular signal-regulated kinase 1/2Apoptosis protein levelsSignal-regulated kinase 1/2ERK kinase 1CDK inhibitor roscovitineIntrinsic apoptosis pathwayHistone deacetylase inhibitor suberoylanilide hydroxamic acidForm of AktProtease-dependent pathwayInhibition of AktTreatment of cellsBak functionBcl-xL expressionCell killingCyclin-dependent kinase inhibitor flavopiridolInhibitor suberoylanilide hydroxamic acidKinase inhibitor flavopiridolERK1/2 functionAkt activityLow-Dose BBR3610 Toxicity in Colon Cancer Cells Is p53-Independent and Enhanced by Inhibition of Epidermal Growth Factor Receptor (ERBB1)-Phosphatidyl Inositol 3 Kinase Signaling
Mitchell C, Kabolizadeh P, Ryan J, Roberts JD, Yacoub A, Curiel DT, Fisher PB, Hagan MP, Farrell NP, Grant S, Dent P. Low-Dose BBR3610 Toxicity in Colon Cancer Cells Is p53-Independent and Enhanced by Inhibition of Epidermal Growth Factor Receptor (ERBB1)-Phosphatidyl Inositol 3 Kinase Signaling. Molecular Pharmacology 2007, 72: 704-714. PMID: 17578896, DOI: 10.1124/mol.107.038406.Peer-Reviewed Original ResearchConceptsColon cancer cellsEpidermal growth factor receptorGrowth factor receptorActive AktC-FLIPMolecular inhibitionCaspase-8 functionsPhosphatidyl inositol 3 kinaseActivation of BaxDominant-negative AktErbB1 inhibitorsFactor receptorHuman colon cancer cellsOverexpression of XIAPCancer cellsSmall moleculesKinase signalingPI3K inhibitorsAkt activityCaspase-9Bcl-xLNull cellsMcl-1SW480 cellsK-rasPhosphatase PTEN is inactivated in bovine aortic endothelial cells exposed to cyclic strain
Hoshino Y, Nishimura K, Sumpio BE. Phosphatase PTEN is inactivated in bovine aortic endothelial cells exposed to cyclic strain. Journal Of Cellular Biochemistry 2007, 100: 515-526. PMID: 16927376, DOI: 10.1002/jcb.21085.Peer-Reviewed Original ResearchConceptsCasein kinase 2Transfection of ECsPTEN plasmidVascular cell morphologyEndothelial cellsPI3K activitySuppression of apoptosisPI3K-Akt pathwayLipid phosphataseMaximal activityPhosphatase PTENPhospho-PTENPTEN activityBovine aortic endothelial cellsIntracellular phosphatidylinositolUpstream regulatorAkt activityKinase 2Phospho-AKT activityK activityTime-dependent mannerAortic endothelial cellsCell morphologyCell proliferationPTEN
2006
Adenoviral vector saturates Akt pro-survival signaling and blocks insulin-mediated rescue of tumor-necrosis-factor-induced apoptosis
Miller-Jensen K, Janes KA, Wong YL, Griffith LG, Lauffenburger DA. Adenoviral vector saturates Akt pro-survival signaling and blocks insulin-mediated rescue of tumor-necrosis-factor-induced apoptosis. Journal Of Cell Science 2006, 119: 3788-3798. PMID: 16940353, DOI: 10.1242/jcs.03102.Peer-Reviewed Original ResearchConceptsCellular responsesGrowth factor stimulationAnti-apoptotic signalsFactor-induced apoptosisAnti-apoptotic signalingCell fatePro-survival signalingSubstrate phosphorylationHuman epithelial cellsProtein kinaseCellular survivalAkt activityMK2 activityMolecular biologyAktAdenoviral vectorKinaseApoptosisEpithelial cellsTNF receptorE1/E3-deleted adenoviral vectorsSignalingGrowth factorRecombinant adenovirusClinical gene therapy
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