Mechanism and Regulation of ERK2 Subcellular Localization

dc.contributor.advisorCobb, Melanie H.en
dc.creatorWhitehurst, Angelique Wrighten
dc.date.accessioned2010-07-12T19:03:13Zen
dc.date.accessioned2014-02-19T21:59:56Z
dc.date.available2010-07-12T19:03:13Zen
dc.date.available2014-02-19T21:59:56Z
dc.date.issued2004-05-04en
dc.description.abstractDynamic changes in the localization of activated proteins can be obligatory events in signaling networks that control cell behavior. ERK1/2 activation contributes to regulated processes such as proliferation, differentiation and survival through the phosphorylation of multiple nuclear and cytoplasmic substrates. The pleiotropic effects of ERK1/2 activation suggest that regulated compartmentalization of the kinases and substrates may contribute to the fidelity of phenotypic changes in response to specific cell stimuli. Therefore, elucidating the mechanism of translocation as well as how this process is controlled is important for understanding how MAP kinases transmit signals. In vitro studies using a permeabilized cell system indicate that nuclear import of ERK2 is not regulated by soluble transport factors, but requires access to nucleoporins. While this process is not influenced by classical import machinery, it can be modulated by anchoring proteins that bind to ERK2 and sequester the kinase in the cytoplasm. One of these proteins, PEA-15, prevents ERK2 import in an in vitro system by inhibiting the kinases' ability to interact with nucleoporins. In vivo assays of phosphorylated ERK1/2 show discrete subcellular localization patterns in response to different stimuli that are independent of the level of ERK1/2 activation. Under conditions in which ERK1/2 is concentrated in the cytoplasm, the nuclear substrate of the kinase, c-Fos, is not expressed, while the cytoplasmic substrate of ERK1/2, p90RSK, is phosphorylated.en
dc.format.digitalOriginborn digitalen
dc.format.mediumElectronicen
dc.format.mimetypeapplication/pdfen
dc.identifier.otheren
dc.identifier.urihttp://hdl.handle.net/2152.5/783en
dc.language.isoenen
dc.subjectMAP Kinase Kinase Kinasesen
dc.subjectCell Physiological Processesen
dc.subjectPhosphorylationen
dc.titleMechanism and Regulation of ERK2 Subcellular Localizationen
dc.type.genredissertationen
dc.type.materialTexten
thesis.date.available2004-05-04en
thesis.degree.departmenten
thesis.degree.disciplineen
thesis.degree.grantorGraduate School of Biomedical Sciencesen
thesis.degree.levelPh.D.en
thesis.degree.nameDoctor of Philosophyen

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