{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T11:01:06Z","timestamp":1790938866619,"version":"4.1.0"},"reference-count":48,"publisher":"Portland Press Ltd.","issue":"2","content-domain":{"domain":["portlandpress.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2011,10,15]]},"abstract":"<jats:p>Lafora 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.<\/jats:p>","DOI":"10.1042\/bj20110150","type":"journal-article","created":{"date-parts":[[2011,7,4]],"date-time":"2011-07-04T15:48:34Z","timestamp":1309794514000},"page":"265-275","update-policy":"https:\/\/doi.org\/10.1042\/crossmark_policy","source":"Crossref","is-referenced-by-count":30,"title":["Laforin, a dual-specificity phosphatase involved in Lafora disease, is phosphorylated at Ser25 by AMP-activated protein kinase"],"prefix":"10.1042","volume":"439","author":[{"given":"Carlos","family":"Rom\u00e1-Mateo","sequence":"first","affiliation":[{"name":"Instituto de Biomedicina de Valencia, CSIC and Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Raras (CIBERER), Jaime Roig 11, 46010 Valencia, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria del Carmen","family":"Solaz-Fuster","sequence":"additional","affiliation":[{"name":"Instituto de Biomedicina de Valencia, CSIC and Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Raras (CIBERER), Jaime Roig 11, 46010 Valencia, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jos\u00e9 Vicente","family":"Gimeno-Alca\u00f1iz","sequence":"additional","affiliation":[{"name":"Instituto de Biomedicina de Valencia, CSIC and Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Raras (CIBERER), Jaime Roig 11, 46010 Valencia, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vikas V.","family":"Dukhande","sequence":"additional","affiliation":[{"name":"Department of Molecular and Cellular Biochemistry and Center for Structural Biology, University of Kentucky, Lexington, KY 40536-0509, U.S.A."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jordi","family":"Donderis","sequence":"additional","affiliation":[{"name":"Instituto de Biomedicina de Valencia, CSIC and Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Raras (CIBERER), Jaime Roig 11, 46010 Valencia, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carolyn A.","family":"Worby","sequence":"additional","affiliation":[{"name":"Departments of Pharmacology, Cellular and Molecular Medicine, and Chemistry and Biochemistry, University of California San Diego, La Jolla, CA 92093-0721, U.S.A."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alberto","family":"Marina","sequence":"additional","affiliation":[{"name":"Instituto de Biomedicina de Valencia, CSIC and Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Raras (CIBERER), Jaime Roig 11, 46010 Valencia, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olga","family":"Criado","sequence":"additional","affiliation":[{"name":"Centro de Investigaciones Biol\u00f3gicas, CSIC and Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Raras (CIBERER), Ramiro de Maeztu 9, 28040 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonius","family":"Koller","sequence":"additional","affiliation":[{"name":"Proteomics Center, SUNY-Stony Brook, School of Medicine, Stony Brook, NY 11794-8691, U.S.A."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Santiago","family":"Rodriguez De Cordoba","sequence":"additional","affiliation":[{"name":"Centro de Investigaciones Biol\u00f3gicas, CSIC and Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Raras (CIBERER), Ramiro de Maeztu 9, 28040 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew S.","family":"Gentry","sequence":"additional","affiliation":[{"name":"Department of Molecular and Cellular Biochemistry and Center for Structural Biology, University of Kentucky, Lexington, KY 40536-0509, U.S.A."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pascual","family":"Sanz","sequence":"additional","affiliation":[{"name":"Instituto de Biomedicina de Valencia, CSIC and Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Raras (CIBERER), Jaime Roig 11, 46010 Valencia, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"288","published-online":{"date-parts":[[2011,9,28]]},"reference":[{"key":"2021112215222452700_B1","doi-asserted-by":"crossref","first-page":"428","DOI":"10.1007\/s11910-007-0066-7","article-title":"Advances in lafora progressive myoclonus epilepsy","volume":"7","author":"Delgado-Escueta","year":"2007","journal-title":"Curr. 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