- Paper Report
- Open Access
TNFR2 activates JNK but not MAPK pathways
- Jean-Noel Gouze1
© Biomed Central Ltd 2002
- Received: 8 January 2002
- Accepted: 8 February 2002
- Published: 8 February 2002
- TNF receptor
Activation of the two tumor necrosis factor (TNF) receptors, p55 type I (TNFR1) and p75 type II (TNFR2), by TNF binding leads to a variety of cellular responses including inflammatory events, proliferation and cell death. Signals induced by these receptors are complex and involve several extracellular signal-regulated kinases (ERKs), including the mitogen-activated protein kinases (MAPKs), c-Jun N-terminal kinases (JNKs) and p38 MAPK. The type and amplitude of cellular response to TNF interaction is thought to be dependent upon the balance of signaling between the two TNF receptors; however, the specific signaling mechanisms of each have not been fully elucidated. In this report the authors studied the ability of signaling via TNFR1 and TNFR2 to activate MAPKs, JNKs and p38 MAPK and the contribution of the two receptors toward cell death processes.
The effects of TNF receptor stimulation were analyzed in several cell lines. The authors showed that stimulation of the various cell lines with wild-type TNF-a or a TNF-a variant specific for the type I receptor (R1-TNF) resulted in full activation of the JNK, MAPK and p38 MAPK pathways. Conversely, TNFR2 stimulation by a TNF-a variant specific for the type II receptor (R2-TNF) and/or a monoclonal antibody with specific agonist activity for TNFR2 (MR2-1) resulted in activation of JNK but not MAPK or p38 MAPK. Analysis of cell death following incubation of the different cell lines with the various TNF variants and the MR2-1 antibody for 24 hours showed that direct, specific TNFR2 stimulation was capable of achieving a complete response, and that the level of cell death mediated by TNFR2 was directly related to its level of expression on the cell surface.
FACS analysis, confocal microscopy, kinase assays, western blot, cell death measurement
- Jupp OJ, McFarlane SM, Anderson HM, Littlejohn AF, Mohamed AA, MacKay RH, Vandenabeele P, MacEwan DJ: Type II tumour necrosis factor alpha receptor (TNFR2) activates c-Jun N-terminal kinase (JNK) but not mitogen-activated protein kinase (MAPK) or p38 pathways. Biochem J. 2001, 359: 525-535.PubMedPubMed CentralView ArticleGoogle Scholar