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dc.contributor.authorKostenko, Sergiy Viktorovich
dc.contributor.authorKhan, Mahmud Tareq Hassan
dc.contributor.authorSylte, Ingebrigt
dc.contributor.authorMoens, Ugo
dc.date.accessioned2012-03-21T08:34:02Z
dc.date.available2012-03-21T08:34:02Z
dc.date.issued2011
dc.description.abstractThe mitogen-activated protein kinase-activated protein kinase MK5 is ubiquitously expressed in vertebrates and is implicated in cell proliferation, cytoskeletal remodeling, and anxiety behavior. This makes MK5 an attractive drug target. We tested several diterpenoid alkaloids for their ability to suppress MK5 kinase activity. We identified noroxoaconitine as an ATP competitor that inhibited the catalytic activity of MK5 in vitro (IC50 = 37.5 μM; K i = 0.675 μM) and prevented PKA-induced nuclear export of MK5, a process that depends on kinase active MK5. MK5 is closely related to MK2 and MK3, and noroxoaconitine inhibited MK3- and MK5- but not MK2-mediated phosphorylation of the common substrate Hsp27. Molecular docking of noroxoaconitine into the ATP binding sites indicated that noroxoaconitine binds more strongly to MK5 than to MK3. Noroxoaconitine and derivatives may help in elucidating the precise biological functions of MK5 and may prove to have therapeutic values.en
dc.identifier.citationCellular and Molecular Life Sciences 68(2011) nr. 2 s. 289-301en
dc.identifier.cristinIDFRIDAID 828522
dc.identifier.doidoi: 10.1007/s00018-010-0452-1
dc.identifier.issn1420-682X
dc.identifier.urihttps://hdl.handle.net/10037/4010
dc.identifier.urnURN:NBN:no-uit_munin_3731
dc.language.isoengen
dc.publisherSpringeren
dc.rights.accessRightsopenAccess
dc.subjectVDP::Mathematics and natural science: 400::Basic biosciences: 470::Biochemistry: 476en
dc.subjectVDP::Matematikk og Naturvitenskap: 400::Basale biofag: 470::Biokjemi: 476en
dc.titleThe diterpenoid alkaloid noroxoaconitine is a Mapkap kinase 5 (MK5/PRAK) inhibitoren
dc.typeJournal articleen
dc.typeTidsskriftartikkelen
dc.typePeer revieweden


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