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c-Jun N-terminal kinases mediate Fas-induced neurite regeneration in PC12 cells.

Authors: Waetzig, V  Loose, K  Haeusgen, W  Herdegen, T 
Citation: Waetzig V, etal., Biochem Pharmacol. 2008 Dec 1;76(11):1476-84. Epub 2008 Jul 19.
Pubmed: (View Article at PubMed) PMID:18692025
DOI: Full-text: DOI:10.1016/j.bcp.2008.07.014

In response to injury, peripheral neuronal cells initiate complex signalling cascades to promote survival and regeneration. In the present study, we used a model of experimental injury in the rat pheochromocytoma cell line PC12 to investigate receptor signals that lead to neurite outgrowth. Nerve growth factor (NGF) dose-dependently induced sprouting and the expression of the NGF receptors Trk tyrosine kinase receptor (TrkA) and p75 neurotrophin receptor (p75(NTR)) as well as Fas and Fas ligand. Neurite regeneration was decreased by chemical inhibition of TrkA, but not p75(NTR), and by the Fas inhibitor protein Fas-Fc. The mitogen-activated protein kinases (MAPKs) extracellular signal-regulated kinase 1/2 (ERK1/2) and c-Jun N-terminal kinases (JNKs) were activated in response to NGF and both significantly contributed to neurite re-growth. Interestingly, otherwise apoptotic Fas ligation supported neuronal recovery exclusively via JNKs and promoted sprouting parallel to NGF. These findings suggest a novel signal integration from the NGF and Fas pathways in the JNK axis of MAPK signalling, where JNKs function as "physiological" mediators of normally apoptotic signals.


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CRRD Object Information
CRRD ID: 2315724
Created: 2010-01-11
Species: All species
Last Modified: 2010-01-11
Status: ACTIVE


RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.