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dc.contributor.authorRomá-Mateo, Carlos-
dc.contributor.authorSolaz-Fuster, Maria Carmen-
dc.contributor.authorGimeno-Alcañiz, José Vicente-
dc.contributor.authorDonderis, Jorge-
dc.contributor.authorMarina, Alberto-
dc.contributor.authorCriado-García, Olga-
dc.contributor.authorRodríguez de Córdoba, Santiago-
dc.contributor.authorSanz, Pascual-
dc.date.accessioned2012-06-04T11:30:09Z-
dc.date.available2012-06-04T11:30:09Z-
dc.date.issued2011-11-01-
dc.identifier.citationBiochemical Journal 439(2):265-75(2011)es_ES
dc.identifier.issn0264-6021-
dc.identifier.urihttp://hdl.handle.net/10261/50695-
dc.descriptionCarlos Romá-Mateo et alt.es_ES
dc.description.abstractLafora progressive myoclonus epilepsy [LD (Lafora disease)] is a fatal autosomal recessive neurodegenerative disorder caused by loss-of-function mutations in either the EPM2A gene, encoding the dual-specificity phosphatase laforin, or the EPM2B gene, encoding the E3-ubiquitin ligase malin. Previously, we and others showed that laforin and malin form a functional complex that regulates multiple aspects of glycogen metabolism, and that the interaction between laforin and malin is enhanced by conditions activating AMPK (AMP-activated protein kinase). In the present study, we demonstrate that laforin is a phosphoprotein, as indicated by two-dimensional electrophoresis, and we identify Ser25 as the residue involved in this modification. We also show that Ser25 is phosphorylated both in vitro and in vivo by AMPK. Lastly, we demonstrate that this residue plays a critical role for both the phosphatase activity and the ability of laforin to interact with itself and with previously established binding partners. The results of the present study suggest that phosphorylation of laforin-Ser25 by AMPK provides a mechanism to modulate the interaction between laforin and malin. Regulation of this complex is necessary to maintain normal glycogen metabolism. Importantly, Ser25 is mutated in some LD patients (S25P), and our results begin to elucidate the mechanism of disease in these patientses_ES
dc.description.sponsorshipThis work was supported the Spanish Ministry of Education and Science [grant number SAF2008-01907 (to P.S.)]; the Generalitat Valenciana [grant number Prometeo 2009/051 (to P.S.)]; the National Institutes of Health [grant numbers R00NS061803, P20RR020171, R01NS070899 (to M.S.G.)]; and the University of Kentucky College of Medicine startup funds (to M.S.G.)es_ES
dc.language.isoenges_ES
dc.publisherPortland Presses_ES
dc.relation.isversionofPostprint-
dc.rightsopenAccesses_ES
dc.subjectAlanine scanning mutagenesises_ES
dc.subjectAMP-activated protein kinase (AMPK)es_ES
dc.subjectGlucan-phosphatasees_ES
dc.subjectLaforines_ES
dc.subjectPhosphorylationes_ES
dc.subjectProtein–protein interactiones_ES
dc.titleLaforin, a dual specificity protein phosphatase involved in Lafora disease, is phosphorylated at Ser25 by AMP-activated protein kinasees_ES
dc.typeartículoes_ES
dc.identifier.doi10.1042/BJ20110150-
dc.description.peerreviewedPeer reviewedes_ES
dc.relation.publisherversionhttp://dx.doi.org/10.1042/BJ20110150es_ES
dc.identifier.e-issn1470-8728-
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