PEA-15 modulates TNFalpha intracellular signaling in astrocytes.
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 TNFalpha-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 TNFalpha outcomes toward survival, whereas its absence allows the development of the cytokine-induced cell death.
Sharif
Ariane
A
INSERM U114, Department de Neuropharmacologie, Collège de France, 75231 Paris Cedex 05, France.
Canton
Brigitte
B
Junier
Marie-Pierre
MP
Chneiweiss
Hervé
H
D000818:Animals; D017209:Apoptosis; D051017:Apoptosis Regulatory Proteins; D001253:Astrocytes / Q000166:cytology / Q000502:physiology*; D001921:Brain / Q000502:physiology; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D010750:Phosphoproteins / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology*; D014158:Transcription, Genetic
D051017:Apoptosis Regulatory Proteins; D047908:Intracellular Signaling Peptides and Proteins; C092039:PEA15 protein, human; D010750:Phosphoproteins; D020928:Mitogen-Activated Protein Kinases