Journal
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Volume 108, Issue 26, Pages 10738-10743Publisher
NATL ACAD SCIENCES
DOI: 10.1073/pnas.1104830108
Keywords
Caenorhabditis elegans; MAPK signaling; laser axotomy
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Funding
- National Science Foundation
- McKnight Endowment Fund for Neuroscience
- Christopher and Dana Reeve Foundation
- Amerisure Charitable Foundation
- Grants-in-Aid for Scientific Research [21247031, 23590331] Funding Source: KAKEN
- Direct For Biological Sciences
- Division Of Integrative Organismal Systems [0950955] Funding Source: National Science Foundation
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Signaling pathways essential for axon regeneration, but not for neuron development or function, are particularly well suited targets for therapeutic intervention. We find that the parallel PMK-3(p38) and KGB-1(JNK) MAPK pathways must be coordinately activated to promote axon regeneration. Axon regeneration fails if the activity of either pathway is absent. These two MAPKs are coregulated by the E3 ubiquitin ligase RPM-1(Phr1) via targeted degradation of the MAPKKKs DLK-1 and MLK-1 and by the MAPK phosphatase VHP-1(MKP7), which negatively regulates both PMK-3 (p38) and KGB-1(JNK).
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