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http://purl.uniprot.org/citations/14976552http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/14976552http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/14976552http://www.w3.org/2000/01/rdf-schema#comment"We recently demonstrated that the LKB1 tumour suppressor kinase, in complex with the pseudokinase STRAD and the scaffolding protein MO25, phosphorylates and activates AMP-activated protein kinase (AMPK). A total of 12 human kinases (NUAK1, NUAK2, BRSK1, BRSK2, QIK, QSK, SIK, MARK1, MARK2, MARK3, MARK4 and MELK) are related to AMPK. Here we demonstrate that LKB1 can phosphorylate the T-loop of all the members of this subfamily, apart from MELK, increasing their activity >50-fold. LKB1 catalytic activity and the presence of MO25 and STRAD are required for activation. Mutation of the T-loop Thr phosphorylated by LKB1 to Ala prevented activation, while mutation to glutamate produced active forms of many of the AMPK-related kinases. Activities of endogenous NUAK2, QIK, QSK, SIK, MARK1, MARK2/3 and MARK4 were markedly reduced in LKB1-deficient cells. Neither LKB1 activity nor that of AMPK-related kinases was stimulated by phenformin or AICAR, which activate AMPK. Our results show that LKB1 functions as a master upstream protein kinase, regulating AMPK-related kinases as well as AMPK. Between them, these kinases may mediate the physiological effects of LKB1, including its tumour suppressor function."xsd:string
http://purl.uniprot.org/citations/14976552http://purl.org/dc/terms/identifier"doi:10.1038/sj.emboj.7600110"xsd:string
http://purl.uniprot.org/citations/14976552http://purl.org/dc/terms/identifier"doi:10.1038/sj.emboj.7600110"xsd:string
http://purl.uniprot.org/citations/14976552http://purl.uniprot.org/core/author"Alessi D.R."xsd:string
http://purl.uniprot.org/citations/14976552http://purl.uniprot.org/core/author"Alessi D.R."xsd:string
http://purl.uniprot.org/citations/14976552http://purl.uniprot.org/core/author"Toth R."xsd:string
http://purl.uniprot.org/citations/14976552http://purl.uniprot.org/core/author"Toth R."xsd:string
http://purl.uniprot.org/citations/14976552http://purl.uniprot.org/core/author"Morrice N.A."xsd:string
http://purl.uniprot.org/citations/14976552http://purl.uniprot.org/core/author"Morrice N.A."xsd:string
http://purl.uniprot.org/citations/14976552http://purl.uniprot.org/core/author"Hardie D.G."xsd:string
http://purl.uniprot.org/citations/14976552http://purl.uniprot.org/core/author"Hardie D.G."xsd:string
http://purl.uniprot.org/citations/14976552http://purl.uniprot.org/core/author"Hawley S.A."xsd:string
http://purl.uniprot.org/citations/14976552http://purl.uniprot.org/core/author"Hawley S.A."xsd:string
http://purl.uniprot.org/citations/14976552http://purl.uniprot.org/core/author"Boudeau J."xsd:string
http://purl.uniprot.org/citations/14976552http://purl.uniprot.org/core/author"Boudeau J."xsd:string
http://purl.uniprot.org/citations/14976552http://purl.uniprot.org/core/author"Deak M."xsd:string
http://purl.uniprot.org/citations/14976552http://purl.uniprot.org/core/author"Deak M."xsd:string
http://purl.uniprot.org/citations/14976552http://purl.uniprot.org/core/author"Goeransson O."xsd:string
http://purl.uniprot.org/citations/14976552http://purl.uniprot.org/core/author"Goeransson O."xsd:string
http://purl.uniprot.org/citations/14976552http://purl.uniprot.org/core/author"Lizcano J.M."xsd:string
http://purl.uniprot.org/citations/14976552http://purl.uniprot.org/core/author"Lizcano J.M."xsd:string
http://purl.uniprot.org/citations/14976552http://purl.uniprot.org/core/author"Maekelae T.P."xsd:string
http://purl.uniprot.org/citations/14976552http://purl.uniprot.org/core/author"Maekelae T.P."xsd:string