Nucleocytoplasmic Localization of MAPKs

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Title: Nucleocytoplasmic Localization of MAPKs
Author: Yazicioglu, Mustafa Naci
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 .
URI: http : / /hdl .handle .net /2152 .5 /647
Date: 2007-08-08

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

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