The NF-kappa B-inducing kinase induces PC12 cell differentiation and prevents apoptosis

J Biol Chem. 2000 Nov 3;275(44):34021-4. doi: 10.1074/jbc.C000507200.


NF-kappa B has been implicated in the survival and differentiation of PC12 cells. In this study, we examined the effect of the NF-kappa B-inducing kinase (NIK) on these processes. When inducibly expressed in PC12 cells, a kinase-proficient but not -deficient form of NIK promoted neurite process formation and mediated anti-apoptotic signaling. As expected, NIK expression led to I kappa B kinase activation and induced nuclear translocation of NF-kappa B. However, NIK-induced neurite outgrowth was only partially blocked by concomitant expression of a nondegradable form of I kappa B alpha that completely blocks NF-kappa B induction. In search of additional signaling pathways activated by NIK, we now demonstrate that NIK activates MEK1 phosphorylation and induces the Erk1/Erk2 MAPK pathway. Treatment of PC12 cells with PD98059, a MEK1 inhibitor, potently blocked neurite process formation; however, a dominantly interfering mutant of the upstream Shc adapter failed to alter this response. These findings reveal a new function for NIK as a MEK1-dependent activator of the MAPK pathway and implicate both the I kappa B kinase and MAPK signaling cascades in NIK-induced differentiation of PC12 cells.

Publication types

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

MeSH terms

  • Animals
  • Apoptosis / physiology*
  • Base Sequence
  • Cell Differentiation / physiology*
  • Oligonucleotides
  • PC12 Cells
  • Phosphorylation
  • Protein Serine-Threonine Kinases / physiology*
  • Rats
  • Signal Transduction


  • Oligonucleotides
  • Protein Serine-Threonine Kinases
  • NF-kappa B kinase