2004
Signaling switches and bistability arising from multisite phosphorylation in protein kinase cascades
Markevich N, Hoek J, Kholodenko B. Signaling switches and bistability arising from multisite phosphorylation in protein kinase cascades. Journal Of Cell Biology 2004, 164: 353-359. PMID: 14744999, PMCID: PMC2172246, DOI: 10.1083/jcb.200308060.Peer-Reviewed Original ResearchConceptsExtracellular signal-regulated kinaseMultisite phosphorylationProtein kinase cascadeBistable switchSignal-regulated kinaseKinase cascadeMAPK cascadeWidespread mechanismDifferent kinasesSame phosphataseProtein kinasePositive feedback loopProtein activityDephosphorylation reactionsCovalent modificationKinaseMAPK phosphorylationFeedback regulationPhosphorylationKinetic propertiesPhosphataseFeedback loopCascade
2001
Temperature Dependence of the Epidermal Growth Factor Receptor Signaling Network Can Be Accounted for by a Kinetic Model †
Moehren G, Markevich N, Demin O, Kiyatkin A, Goryanin I, Hoek JB, Kholodenko BN. Temperature Dependence of the Epidermal Growth Factor Receptor Signaling Network Can Be Accounted for by a Kinetic Model †. Biochemistry 2001, 41: 306-320. PMID: 11772030, DOI: 10.1021/bi011506c.Peer-Reviewed Original ResearchConceptsEpidermal growth factorEGF receptorEGFR kinaseDomain-mediated interactionsEGF receptor dimerizationProtein-protein interactionsRapid tyrosine phosphorylationMultiple signaling proteinsEGFR kinase activityReceptor phosphataseSignaling networksSignaling proteinsProtein interactionsPhosphorylation patternTyrosine phosphorylationReceptor dimerizationKinase activityTarget proteinsMembrane lipidsMolecular termsDephosphorylation reactionsEGFR pathwayPhosphataseKinasePhosphorylation
2000
Diffusion control of protein phosphorylation in signal transduction pathways
KHOLODENKO B, BROWN G, HOEK J. Diffusion control of protein phosphorylation in signal transduction pathways. Biochemical Journal 2000, 350: 901-907. PMID: 10970807, PMCID: PMC1221325, DOI: 10.1042/bj3500901.Peer-Reviewed Original ResearchConceptsProtein phosphorylationProtein kinasePhosphorylation fluxProtein diffusionSignal transduction pathwaysProtein phosphataseSpherical cellsTransduction pathwaysDifferent cellular geometriesCellular locationPlasma membranePlanar membranesKinaseCell membraneCellular geometryProtein diffusion coefficientsPhosphatasePhosphorylationCell centerProteinMembraneCellsSpatial gradientsCytoplasmPathway
1999
Spatial gradients of cellular phospho‐proteins
Brown G, Kholodenko B. Spatial gradients of cellular phospho‐proteins. FEBS Letters 1999, 457: 452-454. PMID: 10471827, DOI: 10.1016/s0014-5793(99)01058-3.Peer-Reviewed Original ResearchConceptsCellular signalingProtein kinaseDifferent cellular geometriesCellular locationPlasma membranePhosphorylated formPlanar membranesProtein diffusionPhosphatase activityKinaseCellular geometryProtein diffusion coefficientsSpatial gradientsSpherical cellsProteinMembraneSuch gradientsCellsSignalingCytoplasmPhosphataseImportant implicationsGradientPotential size