Axon Regeneration Requires Coordinate Activation of p38 and JNK MAPK Pathways

Proc Natl Acad Sci U S A. 2011 Jun 28;108(26):10738-43. doi: 10.1073/pnas.1104830108. Epub 2011 Jun 13.


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).

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Axons*
  • Base Sequence
  • DNA Primers
  • Enzyme Activation
  • MAP Kinase Kinase 4 / metabolism*
  • Nerve Regeneration*
  • Signal Transduction
  • p38 Mitogen-Activated Protein Kinases / metabolism*


  • DNA Primers
  • p38 Mitogen-Activated Protein Kinases
  • MAP Kinase Kinase 4