Overexpression of atypical PKC in PC12 cells enhances NGF-responsiveness and survival through an NF-kappaB dependent pathway

Cell Death Differ. 1999 Aug;6(8):753-64. doi: 10.1038/sj.cdd.4400548.

Abstract

Removal of atypical PKC blocks NGF-induced differentiation of PC12 cells.1 We now examine the consequences that overexpression of atypical PKCs had upon NGF responses. PC12 cells were stably transfected with either PKC-iota or PKC-zeta. Overexpression of atypical PKCs markedly enhanced NGF- induced neurite outgrowth as well as enhanced NGF-stimulated JNK kinase. Cotransfection of HA-JNK1 along with increasing concentrations of PKC-iota, resulted in dose-dependent phosphorylation of GST c-Jun (1 - 79). NGF treatment of PC12 cells resulted in activation of NF-kappaB. In comparison, overexpression of atypical PKC-iota was by itself sufficient to activate NF-kappaB and shift the kinetics of NGF-induced kappaB activity. Furthermore, transfection of full-length antisense PKC-iota blocked basal and NGF-stimulated NF-kappaB. Differentiated and undifferentiated PC12 cells overexpressing atypical PKC-iota were protected from serum deprivation-induced cell death. Collectively, these findings demonstrate that atypical PKC-iota lies in a pathway that regulates NF-kappaB and contributes to both neurotrophin-mediated differentiation and survival signaling.

Publication types

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

MeSH terms

  • Animals
  • Cell Survival
  • Gene Expression
  • Isoenzymes / biosynthesis*
  • Isoenzymes / genetics
  • JNK Mitogen-Activated Protein Kinases
  • Mitogen-Activated Protein Kinases / metabolism
  • NF-kappa B / metabolism*
  • Nerve Growth Factor / metabolism*
  • Nerve Growth Factor / pharmacology
  • PC12 Cells
  • Protein Kinase C / biosynthesis*
  • Protein Kinase C / genetics
  • Rats
  • Signal Transduction*

Substances

  • Isoenzymes
  • NF-kappa B
  • Nerve Growth Factor
  • protein kinase C zeta
  • Protein Kinase C
  • protein kinase C lambda
  • JNK Mitogen-Activated Protein Kinases
  • Mitogen-Activated Protein Kinases