Nucleocytoplasmic Localization of MAPKs

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dc.contributor.advisor Cobb , Melanie H . en
dc.creator Yazicioglu , Mustafa Naci en 2010 -07 -12T18 :43 :39Z en 2014 -02 -19T22 :00 :47Z 2010 -07 -12T18 :43 :39Z en 2014 -02 -19T22 :00 :47Z 2007 -08 -08 en
dc.identifier.other 756837526 en
dc.identifier.uri http : / /hdl .handle .net /2152 .5 /647 en
dc.description.abstract Mitogen -activated protein kinases (MAPKs ) comprise a family of protein -serine /threonine kinases , which participate in signal transduction pathways that control intracellular events . MAPKs are regulated by phosphorylation cascades , which are usually initiated by external stimuli including a variety of ligands . At least two upstream protein kinases are activated in series to lead to activation of a MAPK . The kinase that activates the MAPK is a MAPK kinase (MAP2K or MEK ) and the kinase that phosphorylates the MAP2K is a MAP3K or MEK kinase (MEKK ) . Upon activation , MAPKs may translocate to the nucleus to phosphorylate nuclear targets . Previous findings from our laboratory showed that a constitutively active and nuclear form of the MAPK ERK2 is sufficient for transformation of immortalized fibroblasts (Robinson MJ et al ,1998 ) . However the mechanisms of nuclear localization of MAPKs are still not fully understood clearly . Although most nucleocytoplasmic localization events require carrier proteins known as karyopherins (importins and exportins ) , ERK2 enters the nucleus of permeabilized cells even if these carrier proteins are missing . This is explained by direct binding to proteins in the nuclear pore complex (NPC ) . Similar to ERK2 targets , NPC proteins also contain Phe -Xxx -Phe (FXF ) motifs . My first aim in this project was to examine the roles of ERK2 residues that are crucial for FXF binding on nuclear localization of ERK2 . Mutating these ERK2 residues decreased the nuclear import of ERK2 proteins in permeabilized cells . Secondly , the regulation of ERK2 nuclear export was analyzed . It was observed that ERK2 export occurs by two distinct processes ; one energy -dependent and the other energy -independent . My final aim was analyzing the activation and nucleocytoplasmic trafficking of other MAPKs , JNK and p38 . en
dc.format.medium Electronic en
dc.format.mimetype application /pdf en
dc.language.iso en en
dc.subject Amino Acid Substitution en
dc.subject Cell Nucleus en
dc.subject Mitogen -Activated Protein Kinase 1 en
dc.subject Nuclear Pore Complex Proteins en
dc.title Nucleocytoplasmic Localization of MAPKs en
dc.type.genre dissertation en
dc.type.material Text en Doctor of Philosophy en Ph .D . en Cell Regulation en Graduate School of Biomedical Sciences en en
dc.format.digitalOrigin born digital en 2008 -08 -08 en


Nucleocytoplasmic Localization of MAPKs. Graduate School of Biomedical Sciences. Available electronically from http : / /hdl .handle .net /2152 .5 /647 .

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