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dc.contributor.authorChen, Fenghao
dc.contributor.authorSarabipour, Sarvenaz
dc.contributor.authorHristova, Kalina
dc.date.accessioned2014-04-02T12:22:04Z
dc.date.available2014-04-02T12:22:04Z
dc.date.issued2013-02-20
dc.identifier.citationdoi: 10.1371/journal.pone.0056521en_US
dc.identifier.issn1932-6203
dc.identifier.urihttp://jhir.library.jhu.edu/handle/1774.2/36732
dc.descriptionPMC3577887en_US
dc.description.abstractThe A391E mutation in fibroblast growth factor receptor 3 (FGFR3) is the genetic cause for Crouzon syndrome with Acanthosis Nigricans. Here we investigate the effect of this mutation on FGFR3 activation in HEK 293 T cells over a wide range of fibroblast growth factor 1 concentrations using a physical-chemical approach that deconvolutes the effects of the mutation on dimerization, ligand binding, and efficiency of phosphorylation. It is believed that the mutation increases FGFR3 dimerization, and our results verify this. However, our results also demonstrate that the increase in dimerization is not the sole effect of the mutation, as the mutation also facilitates the phosphorylation of critical tyrosines in the activation loop of FGFR3. The activation of mutant FGFR3 is substantially increased due to a combination of these two effects. The low expression of the mutant, however, attenuates its signaling and may explain the mild phenotype in Crouzon syndrome with Acanthosis Nigricans. The results presented here provide new knowledge about the physical basis behind growth disorders and highlight the fact that a single RTK mutation may affect multiple steps in RTK activation.en_US
dc.description.sponsorshipJH Libraries Open Access Funden_US
dc.language.isoen_USen_US
dc.publisherPLoS Organizationen_US
dc.relation.ispartofseriesPLoS ONE;v. 8 no. 2 p. e56521
dc.subjectReceptor, Fibroblast Growth Factor, Type 3en_US
dc.subjectCraniofacial Dysostosisen_US
dc.subjectAmino Acid Substitutionen_US
dc.subjectAcanthosis Nigricansen_US
dc.titleMultiple Consequences of a Single Amino Acid Pathogenic RTK Mutation: The A391E Mutation in FGFR3en_US
dc.typeArticleen_US


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