The Fas-associated death domain protein/caspase-8/c-FLIP signaling pathway is involved in TNF-induced activation of ERK

Journal Article · Sat Oct 15 00:00:00 EDT 2005 · Experimental Cell Research

DOI:https://doi.org/10.1016/j.yexcr.2005.07.022· OSTI ID:20717665

Lueschen, Silke ^[1]; Falk, Markus ^[1]; Scherer, Gudrun ^[1]; Ussat, Sandra ^[1]; Paulsen, Maren ^[1]; Adam-Klages, Sabine ^[1]

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1. Institut fuer Immunologie, Universitaetsklinikum Schleswig-Holstein Campus Kiel, Michaelisstrasse 5, 24105 Kiel (Germany)

The cytokine TNF activates multiple signaling pathways leading to cellular responses ranging from proliferation and survival to apoptosis. While most of these pathways have been elucidated in detail over the past few years, the molecular mechanism leading to the activation of the MAP kinases ERK remains ill defined and is controversially discussed. Therefore, we have analyzed TNF-induced ERK activation in various human and murine cell lines and show that it occurs in a cell-type-specific manner. In addition, we provide evidence for the involvement of the signaling components Fas-associated death domain protein (FADD), caspase-8, and c-FLIP in the pathway activating ERK in response to TNF. This conclusion is based on the following observations: (I) Overexpression of FADD, caspase-8, or a c-FLIP protein containing the death effector domains only leads to enhanced and prolonged ERK activation after TNF treatment. (II) TNF-induced ERK activation is strongly diminished in the absence of FADD. Interestingly, the enzymatic function of caspase-8 is not required for TNF-induced ERK activation. Additional evidence suggests a role for this pathway in the proliferative response of murine fibroblasts to TNF.

• OSTI ID: 20717665
• Journal Information: Experimental Cell Research, Vol. 310, Issue 1; Other Information: DOI: 10.1016/j.yexcr.2005.07.022; PII: S0014-4827(05)00324-1; Copyright (c) 2005 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved; Country of input: International Atomic Energy Agency (IAEA); ISSN 0014-4827
• Country of Publication: United States
• Language: English

Related Subjects

60 APPLIED LIFE SCIENCES
APOPTOSIS
CELL PROLIFERATION
DEATH
FIBROBLASTS
MBP
MYELIN
PHOSPHOTRANSFERASES
RECEPTORS