English   español  
Please use this identifier to cite or link to this item: http://hdl.handle.net/10261/50695
Share/Impact:
Statistics
logo share SHARE logo core CORE   Add this article to your Mendeley library MendeleyBASE

Visualizar otros formatos: MARC | Dublin Core | RDF | ORE | MODS | METS | DIDL
Exportar a otros formatos:
Title

Laforin, a dual specificity protein phosphatase involved in Lafora disease, is phosphorylated at Ser25 by AMP-activated protein kinase

AuthorsRomá-Mateo, Carlos ; Solaz-Fuster, Maria Carmen ; Gimeno-Alcañiz, José Vicente; Donderis, Jorge ; Marina, Alberto ; Criado-García, Olga ; Rodríguez de Córdoba, Santiago ; Sanz, Pascual
KeywordsAlanine scanning mutagenesis
AMP-activated protein kinase (AMPK)
Glucan-phosphatase
Laforin
Phosphorylation
Protein–protein interaction
Issue Date1-Nov-2011
PublisherPortland Press
CitationBiochemical Journal 439(2):265-75(2011)
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 patients
DescriptionCarlos Romá-Mateo et alt.
Publisher version (URL)http://dx.doi.org/10.1042/BJ20110150
URIhttp://hdl.handle.net/10261/50695
DOI10.1042/BJ20110150
ISSN0264-6021
E-ISSN1470-8728
Appears in Collections:(IBV) Artículos
(CIB) Artículos
Files in This Item:
File Description SizeFormat 
lafora_disease_Roma.pdf151,69 kBAdobe PDFThumbnail
View/Open
Show full item record
Review this work
 

Related articles:


WARNING: Items in Digital.CSIC are protected by copyright, with all rights reserved, unless otherwise indicated.