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dc.contributor.advisorMoens, Ugo
dc.contributor.advisorKostenko, Sergiy
dc.contributor.authorLægreid, Kari Jenssen
dc.date.accessioned2011-06-21T07:46:43Z
dc.date.available2011-06-21T07:46:43Z
dc.date.issued2011-05-02
dc.description.abstractThe mitogen activated protein kinases (MAPK) are a large and diverse family of protein kinases, contributing to the cells ability to respond to external stimuli by relaying messages in a well orchestrated way until they reach their final destinations. This is achieved through successive phosphorylation events. One member of this large family is mitogen activated protein kinase activated protein kinase 5 (MAPKAPK5/MK5), which is activated by the upstream atypical MAPKs extracellular signal-regulated kinases 3 and 4 (ERK3 and ERK4), and possibly also the conventional MAPK p38MAPK. MK5 has been shown to be implicated in F-actin rearrangement through phosphorylation of heat shock protein 27 (HSP27), tumor suppression through at least two different pathways and cell cycle arrest in response to energy depletion. There has been done relatively little research on this protein, and few bona fide substrates for MK5 are known, although knowledge is emerging. One possible interaction partner for MK5 is DNAJB1, which has been shown to be phosphorylated by MK5 in vitro. DNAJB1 is a member of the heat shock protein 40 (HSP40) family/DNAJ family, which is a subunit of the much larger heat shock protein superfamily. Heat shock proteins mostly function as chaperones and co-chaperones in the cell, assisting in the maintenance of protein homeostasis, by refolding or degrading misfolded proteins. Conditions of stress in the cell can lead to increased levels of misfolded proteins, which in turn are thought to initiate the increased transcription of heat shock proteins observed in stressed cells. DNAJB1 mainly serves as a co-chaperone for heat shock protein 70, and has been implicated to play a role in various types of cancer and neurodegenerative disorders. In this study we demonstrated that MK5 phosphorylates DNAJB1 in vitro, and that Tyrosine residue 6 and Serine residues 149, 151 and 171 in DNAJB1 are in vitro phosphorylation sites for MK5. Our results also indicate that other phosphorylation sites may be present. Further experiments are needed to elucidate the in vivo potential of these phosphoacceptor sites. We also found that MK5 and DNAJB1 exist in complexes. This interaction proved hard to reproduce, indicating that it might be of a transient nature, or perhaps a product of non-physiological conditions. We also showed that both proteins localize mainly to the nucleus in resting cells, when ectopically expressed, and that DNAJB1 seems to downregulate the level or the transcriptional activity of MK5 when both proteins are ectopically expressed in the cell.en
dc.identifier.urihttps://hdl.handle.net/10037/3427
dc.identifier.urnURN:NBN:no-uit_munin_3149
dc.language.isoengen
dc.publisherUniversitetet i Tromsøen
dc.publisherUniversity of Tromsøen
dc.rights.accessRightsopenAccess
dc.rights.holderCopyright 2011 The Author(s)
dc.rights.urihttps://creativecommons.org/licenses/by-nc-sa/3.0en_US
dc.rightsAttribution-NonCommercial-ShareAlike 3.0 Unported (CC BY-NC-SA 3.0)en_US
dc.subject.courseIDMBI-3910en
dc.subjectVDP::Matematikk og Naturvitenskap: 400::Basale biofag: 470::Molekylærbiologi: 473en
dc.subjectVDP::Mathematics and natural science: 400::Basic biosciences: 470::Molecular biology: 473en
dc.subjectVDP::Matematikk og Naturvitenskap: 400::Basale biofag: 470::Cellebiologi: 471en
dc.subjectVDP::Mathematics and natural science: 400::Basic biosciences: 470::Cell biology: 471en
dc.subjectVDP::Matematikk og Naturvitenskap: 400::Basale biofag: 470::Biokjemi: 476en
dc.subjectVDP::Mathematics and natural science: 400::Basic biosciences: 470::Biochemistry: 476en
dc.subjectVDP::Medisinske Fag: 700::Basale medisinske, odontologiske og veterinærmedisinske fag: 710::Medisinsk mikrobiologi: 715en
dc.subjectVDP::Medical disciplines: 700::Basic medical, dental and veterinary science disciplines: 710::Medical microbiology: 715en
dc.subjectVDP::Medisinske Fag: 700::Basale medisinske, odontologiske og veterinærmedisinske fag: 710::Medisinsk molekylærbiologi: 711en
dc.subjectVDP::Medical disciplines: 700::Basic medical, dental and veterinary science disciplines: 710::Medical molecular biology: 711en
dc.subjectVDP::Medisinske Fag: 700::Basale medisinske, odontologiske og veterinærmedisinske fag: 710::Medisinsk biokjemi: 726en
dc.subjectVDP::Medical disciplines: 700::Basic medical, dental and veterinary science disciplines: 710::Medical biochemistry: 726en
dc.titleA study of the interaction between MAPKAP Kinase 5 / MK5 and DNAJB1en
dc.typeMaster thesisen
dc.typeMastergradsoppgaveen


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Attribution-NonCommercial-ShareAlike 3.0 Unported (CC BY-NC-SA 3.0)
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