Featured Publications
EGFR Ligands Differentially Stabilize Receptor Dimers to Specify Signaling Kinetics
Freed DM, Bessman NJ, Kiyatkin A, Salazar-Cavazos E, Byrne PO, Moore JO, Valley CC, Ferguson KM, Leahy DJ, Lidke DS, Lemmon MA. EGFR Ligands Differentially Stabilize Receptor Dimers to Specify Signaling Kinetics. Cell 2017, 171: 683-695.e18. PMID: 28988771, PMCID: PMC5650921, DOI: 10.1016/j.cell.2017.09.017.Peer-Reviewed Original ResearchConceptsReceptor tyrosine kinasesEpidermal growth factor receptorEGFR ligandsEGFR extracellular regionG protein-coupled receptorsDifferent EGFR ligandsCellular programsDifferent activating ligandsEGFR dimersCell signalingGrowth factor receptorExtracellular regionDimeric conformationEGFR dimerizationNew therapeutic opportunitiesReceptor dimersTyrosine kinaseBreast cancer cellsDimerization strengthActivating ligandsFactor receptorCancer cellsEpigenTherapeutic opportunitiesBiased agonism
2016
Bistability in the Rac1, PAK, and RhoA Signaling Network Drives Actin Cytoskeleton Dynamics and Cell Motility Switches
Byrne KM, Monsefi N, Dawson JC, Degasperi A, Bukowski-Wills JC, Volinsky N, Dobrzyński M, Birtwistle MR, Tsyganov MA, Kiyatkin A, Kida K, Finch AJ, Carragher NO, Kolch W, Nguyen LK, von Kriegsheim A, Kholodenko BN. Bistability in the Rac1, PAK, and RhoA Signaling Network Drives Actin Cytoskeleton Dynamics and Cell Motility Switches. Cell Systems 2016, 2: 38-48. PMID: 27136688, PMCID: PMC4802415, DOI: 10.1016/j.cels.2016.01.003.Peer-Reviewed Original ResearchConceptsPAK inhibitionMesenchymal breast cancer cellsCell migrationActin cytoskeleton dynamicsRho small GTPase familyRac1 activation levelsSmall GTPase familySwitch-like responsePAK family kinasesSmall chemical inhibitorsCytoskeleton dynamicsActin dynamicsGTPase familyFamily kinasesGTPase activityBistable fashionInhibitory crosstalkChemical inhibitorsBreast cancer cellsMass spectrometry-based quantitationRac1RhoACell morphologyCancer cellsPAK
2011
Prolactin-stimulated activation of ERK1/2 mitogen-activated protein kinases is controlled by PI3-kinase/Rac/PAK signaling pathway in breast cancer cells
Aksamitiene E, Achanta S, Kolch W, Kholodenko BN, Hoek JB, Kiyatkin A. Prolactin-stimulated activation of ERK1/2 mitogen-activated protein kinases is controlled by PI3-kinase/Rac/PAK signaling pathway in breast cancer cells. Cellular Signalling 2011, 23: 1794-1805. PMID: 21726627, PMCID: PMC3156300, DOI: 10.1016/j.cellsig.2011.06.014.Peer-Reviewed Original ResearchMeSH KeywordsBreastBreast NeoplasmsCell Line, TumorFemaleGene Expression Regulation, NeoplasticGene SilencingHumansImmunoprecipitationMitogen-Activated Protein KinasesP21-Activated KinasesPhosphatidylinositol 3-KinasesPhosphorylationProlactinProtein BindingProto-Oncogene Proteins c-aktReal-Time Polymerase Chain ReactionRNA, Small InterferingSignal TransductionTransfectionConceptsBreast cancer cellsExtracellular signal-regulated kinases ERK1PI3-kinase/Akt pathwayDistinct signal transduction pathwaysERK1/2 mitogen-activated protein kinasesRac/PAK pathwayCancer cellsMitogen-activated protein kinaseSignal transduction pathwaysKinase/AktPDK1/AktJAK/STATSiRNA-mediated suppressionMAPK/ERKJAK2/STAT5MAPK signaling pathwaysRegulatory circuitsFAK activityKinases ERK1PAK pathwaySrc familyProtein interactionsProtein kinaseTransduction pathwaysPhosphoinositide 3THE ROUTES OF ERK ACTIVATION IN PROLACTIN‐STIMULATED BREAST CANCER CELLS
Aksamitiene E, Achanta S, Kiyatkin A, Hoek J. THE ROUTES OF ERK ACTIVATION IN PROLACTIN‐STIMULATED BREAST CANCER CELLS. The FASEB Journal 2011, 25: 946.1-946.1. DOI: 10.1096/fasebj.25.1_supplement.946.1.Peer-Reviewed Original ResearchJanus kinase/signal transducerDistinct signal transduction pathwaysRac/PAK pathwayBreast cancer cellsKinase/signal transducerRas/mitogenSignal transduction pathwaysActivator of transcriptionKinase/AktTotal cell lysatesActivity of JAK2Cancer cellsPI3K/AktAdaptor proteinShc familyPAK pathwaySrc familyProtein kinaseTransduction pathwaysTyrosine phosphorylationC-RafPhosphoinositide 3Cancer cell proliferationSignal transducerMAPK signaling
2010
PI3K/Akt-sensitive MEK-independent compensatory circuit of ERK activation in ER-positive PI3K-mutant T47D breast cancer cells
Aksamitiene E, Kholodenko BN, Kolch W, Hoek JB, Kiyatkin A. PI3K/Akt-sensitive MEK-independent compensatory circuit of ERK activation in ER-positive PI3K-mutant T47D breast cancer cells. Cellular Signalling 2010, 22: 1369-1378. PMID: 20471474, PMCID: PMC2893265, DOI: 10.1016/j.cellsig.2010.05.006.Peer-Reviewed Original ResearchMeSH KeywordsBreast NeoplasmsCarcinoma, Ductal, BreastCell Line, TumorEpidermal Growth FactorExtracellular Signal-Regulated MAP KinasesFemaleHumansIntercellular Signaling Peptides and ProteinsMAP Kinase Signaling SystemMitogen-Activated Protein Kinase KinasesMutationPhosphatidylinositol 3-KinasesPhosphoinositide-3 Kinase InhibitorsProtein Serine-Threonine KinasesProto-Oncogene Proteins c-aktReceptors, EstrogenConceptsERK activationERK phosphorylationEpidermal growth factorRas/mitogen-activated protein kinase cascadeMitogen-activated protein kinase cascadeEGF-induced ERK phosphorylationT47D breast cancer cellsBreast cancer cellsProtein kinase cascadeErbB-family ligandsClass I PI3KMCF7 cellsCancer cellsErbB receptor ligandsSmall molecule inhibitorsPI3K/AktKinase cascadeProtein kinasePI3K inhibitionCandidate proteinsPD 098059Cellular growthCell survivalFamily ligandsMolecule inhibitorsDynamic cross‐talk between PI3‐kinase/Akt and Ras/ERK pathways in EGF receptor signaling that can affect drug sensitivity in tumor cells
Aksamitiene E, Kiyatkin A, Hoek J. Dynamic cross‐talk between PI3‐kinase/Akt and Ras/ERK pathways in EGF receptor signaling that can affect drug sensitivity in tumor cells. The FASEB Journal 2010, 24: 715.2-715.2. DOI: 10.1096/fasebj.24.1_supplement.715.2.Peer-Reviewed Original ResearchPI3KRas/ERK pathwayPI3-kinase/AktPI3K activityEGF dose-dependent mannerNegative feedback loopAdaptor proteinMitogenic signalingU0126 inhibitorIndependent parallel pathwaysERK activityEGF receptorERK pathwayCell survivalK activityReciprocal crosstalkERK responseRecruitment mechanismsPhosphorylated ERKImmunoblot analysisEGF dosesERKAkt expressionSubcellular fractionsCancer cells