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 3
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 inhibitors
2006
Scaffolding Protein Grb2-associated Binder 1 Sustains Epidermal Growth Factor-induced Mitogenic and Survival Signaling by Multiple Positive Feedback Loops*
Kiyatkin A, Aksamitiene E, Markevich NI, Borisov NM, Hoek JB, Kholodenko BN. Scaffolding Protein Grb2-associated Binder 1 Sustains Epidermal Growth Factor-induced Mitogenic and Survival Signaling by Multiple Positive Feedback Loops*. Journal Of Biological Chemistry 2006, 281: 19925-19938. PMID: 16687399, PMCID: PMC2312093, DOI: 10.1074/jbc.m600482200.Peer-Reviewed Original ResearchConceptsEpidermal growth factorRas/MAPK signalingGab1 tyrosine phosphorylationGrowth factorRole of Gab1PI3K/Akt activationMultiple positive feedback loopsProtein Grb2Mutant proteinsScaffold proteinTyrosine phosphorylationBinder 1Positive feedback loopMitogenic pathwaysMAPK signalingEssential functionsSurvival signalingDiverse perturbationsCellular responsesAkt activationCytokine receptorsPharmacological inhibitorsGab1EGF dosesGrb2