Role of MEKK2 Phosphorylation at Threonine 263 on SMYD3-Mediated Methylation of Lysine 260

dc.contributor.advisorScheid, Michael
dc.contributor.authorCorridore, Rachel Nicole
dc.date.accessioned2024-07-18T21:24:05Z
dc.date.available2024-07-18T21:24:05Z
dc.date.copyright2024-04-17
dc.date.issued2024-07-18
dc.date.updated2024-07-18T21:24:04Z
dc.degree.disciplineBiology
dc.degree.levelMaster's
dc.degree.nameMSc - Master of Science
dc.description.abstractMEKK2 is a protein serine/threonine-kinase involved in the activation of many MAP-kinase signalling pathways. In a previous study, SMYD3-mediated methylation at K260 of MEKK2 was demonstrated to promote aberrant input downstream of oncogenic Ras-signaling, promoting Ras-driven PDAC and LAC progression. Our lab has previously characterized the role of MEKK2 phosphorylation at T283 and has recently discovered a novel second phosphorylation site at T263. We show that together, these sites form the bipartite binding group for 14-3-3 adapter proteins. This study focuses on characterizing T263 and T283 as regulatory phosphosites in K260 methylation and implicates 14-3-3 as a promoting factor in facilitating SMYD3-mediated methylation at K260. Our findings provide a potential mechanism of MEKK2 oncogenic function, whereby 14-3-3 preserves phosphorylation at T263 and T283, together promoting K260 methylation and MEKK2 activation. Our study characterizes T263 and T283 of MEKK2 and 14-3-3 phosphoadapter proteins as potential therapeutic targets in PDAC and LAC.
dc.identifier.urihttps://hdl.handle.net/10315/42172
dc.languageen
dc.rightsAuthor owns copyright, except where explicitly noted. Please contact the author directly with licensing requests.
dc.subjectMolecular biology
dc.subjectCellular biology
dc.subject.keywordsMEKK2
dc.subject.keywordsSMYD3
dc.subject.keywordsPDAC
dc.subject.keywordsLAC
dc.subject.keywordsK260
dc.subject.keywordsT263
dc.subject.keywordsT283
dc.subject.keywordsMAPK
dc.subject.keywordsMAP3K2
dc.subject.keywordsMEKK3
dc.subject.keywordsMAP3K3
dc.subject.keywords14-3-3
dc.subject.keywordsMolecular biology
dc.subject.keywordsCellular biology
dc.subject.keywordsCancer biology
dc.subject.keywordsCancer research
dc.subject.keywordsPancreatic cancer
dc.subject.keywordsPancreatic ductal adenocarcinoma
dc.subject.keywordsLung cancer
dc.subject.keywordsLung adenocarcinoma
dc.subject.keywordsLysine 260
dc.subject.keywordsThreonine 263
dc.subject.keywordsThreonine 283
dc.subject.keywordsLysine methylation
dc.subject.keywordsLysine methyltransferase
dc.subject.keywordsMitogen-activated protein kinase
dc.subject.keywordsKinase
dc.subject.keywordsRas
dc.subject.keywordsOncogene
dc.subject.keywordsTumorigenesis
dc.subject.keywordsOncogenic
dc.subject.keywordsRas pathway
dc.subject.keywordsSignalling pathway
dc.subject.keywordsCell signalling
dc.subject.keywordsMAPK signalling
dc.titleRole of MEKK2 Phosphorylation at Threonine 263 on SMYD3-Mediated Methylation of Lysine 260
dc.typeElectronic Thesis or Dissertation

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