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PEA-15 Modulates TNF Intracellular Signaling in Astrocytes
INSERM U114, Department de Neuropharmacologie, Collège de France, 75231 Paris Cedex 05, France
Address for correspondence: Hervé Chneiweiss, INSERM U114, Chair de Neuropharmacologie, Collège de France, 11 Place M. Berthelot, 75231 Paris Cedex 05, France. Voice: 33-1 44 27 12 19; fax: 33-1 44 27 12 60. herve.chneiweiss{at}college-de-france.fr Ann. N.Y. Acad. Sci. 1010: 43-50 (2003).
PEA-15 is a small protein (15 kDa) that was first identified as an abundant phosphoprotein in brain astrocytes and subsequently shown to be widely expressed in different tissues and highly conserved among mammals. It is composed of an N-terminal death effector domain (DED) and a C-terminal tail of irregular structure. PEA-15 is regulated by multiple calcium-dependent phosphorylation pathways. PEA-15 is ideally positioned to play a major role in signal integration. Accordingly, it has been demonstrated that PEA-15 diverts astrocytes from TNF
-triggered apoptosis and regulates the actions of the ERK MAP kinase cascade by binding to ERK and altering its subcellular localization. Expression of PEA-15 directs TNF outcomes toward survival, whereas its absence allows the development of the cytokine-induced cell death.
Key Words: PEA-15 TNFalpha death effector domain NF- B ERK MAP kinaseThis article has been cited by other articles:
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