Activation of ERK1/2 and cPLA(2) by the p55 TNF receptor occurs independently of FAN

Citation
S. Luschen et al., Activation of ERK1/2 and cPLA(2) by the p55 TNF receptor occurs independently of FAN, BIOC BIOP R, 274(2), 2000, pp. 506-512
Citations number
41
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Biochemistry & Biophysics
Journal title
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
ISSN journal
0006-291X → ACNP
Volume
274
Issue
2
Year of publication
2000
Pages
506 - 512
Database
ISI
SICI code
0006-291X(20000802)274:2<506:AOEACB>2.0.ZU;2-1
Abstract
The generation of proinflammatory eicosanoids in response to tumor necrosis factor (TNF) involves the activation of cytosolic phospholipase A(2) (cPLA (2)), presumably by phosphorylation through extracellular signal-regulated kinases (ERR), Earlier results had suggested that a pathway involving the p 55 TNF receptor (TNF-R55), neutral sphingomyelinase (N-SMase), and c-Raf-l activates ERK and cPLA(2). We have previously shown that a cytoplasmic regi on of TNF-R55 distinct from the death domain regulates the activation of N- SMase through binding of the adapter protein FAN. Analysis of embryonal fib roblasts from FAN knockout mice revealed that TNF-induced activation of bot h ERK and cPLA(2) occurs without involvement of FAN. Furthermore, we provid e evidence that the TNF-dependent activation of ERK and cPLA(2) requires th e intact death domain of TNF-R55. Finally, we demonstrate that in murine fi broblasts cPLA(2) is phosphorylated in response to TNF solely by ERK, but n ot by p38 mitogen-activated protein kinase, suggesting a signaling pathway from TNF-R55 via the death domain to ERK and cPLA(2). (C) 2000 Academic Pre ss.