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MEKK1 controls neurite regrowth after experimental injury by balancing ERK1/2 and JNK2 signaling.

Authors: Waetzig, V  Herdegen, T 
Citation: Waetzig V and Herdegen T, Mol Cell Neurosci. 2005 Sep;30(1):67-78.
Pubmed: (View Article at PubMed) PMID:16006144
DOI: Full-text: DOI:10.1016/j.mcn.2005.06.001

After injury, peripheral neuronal cells initiate complex signaling cascades to promote survival and regeneration. In the present study, we have identified the mitogen-activated protein kinase (MAPK) isoforms which are necessary for nerve growth factor (NGF)-induced neurite regrowth after injury of differentiated PC12 cells. Extracellular signal-regulated kinases 1 and 2 (ERK1/2) and the usually pro-apoptotic c-Jun N-terminal kinase 2 (JNK2) are crucial for neurite regrowth, while p38 plays no role in this context. Surprisingly, the MEK1 inhibitors PD 98059 and U 0126 blocked both ERK1/2 and JNK phosphorylation, indicating a novel form of balancing MAPK cascade cross-talk. Results from RNAi experiments excluded direct ERK/JNK interactions. We identified the upstream kinase MEKK1 as an activator of both the ERK1/2 and JNK2 pathways, whereby the ERK1/2 kinase MEK1 and the JNK kinase MKK7 bind to MEKK1 in a competing fashion. Our findings suggest an important role of JNK2 and MAPK pathway cross-talk in neurite regeneration.

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CRRD Object Information
CRRD ID: 2293486
Created: 2008-05-29
Species: All species
Last Modified: 2008-05-29
Status: ACTIVE



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