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Induction of neurites by the regulatory domains of PKCdelta and epsilon is counteracted by PKC catalytic activity and by the RhoA pathway.

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Author

Summary, in English

We have shown that protein kinase C (PKC) var epsilon, independently of its kinase activity, via its regulatory domain (RD), induces neurites in neuroblastoma cells. This study was designed to evaluate whether the same effect is obtained in nonmalignant neural cells and to dissect mechanisms mediating the effect. Overexpression of PKCvar epsilon resulted in neurite induction in two immortalised neural cell lines (HiB5 and RN33B). Phorbol ester potentiated neurite outgrowth from PKCvar epsilon-overexpressing cells and led to neurite induction in cells overexpressing PKCδ. The effects were potentiated by blocking the PKC catalytic activity with GF109203X. Furthermore, kinase-inactive PKCδ induced more neurites than the wild-type isoform. The isolated regulatory domains of novel PKC isoforms also induced neurites. Experiments with PKCδ-overexpressing HiB5 cells demonstrated that phorbol ester, even in the presence of a PKC inhibitor, led to a decrease in stress fibres, indicating an inactivation of RhoA. Active RhoA blocked PKC-induced neurite outgrowth, and inhibition of the RhoA effector ROCK led to neurite outgrowth. This demonstrates that neurite induction by the regulatory domain of PKCδ can be counteracted by PKCδ kinase activity, that PKC-induced neurite outgrowth is accompanied by stress fibre dismantling indicating an inactivation of RhoA, and that the RhoA pathway suppresses PKC-mediated neurite outgrowth.

Publishing year

2004

Language

English

Pages

135-150

Publication/Series

Experimental Cell Research

Volume

292

Issue

1

Document type

Journal article

Publisher

Academic Press

Topic

  • Neurosciences
  • Cancer and Oncology

Keywords

  • RhoA
  • Neurite outgrowth
  • Protein kinase C
  • Stress fibres

Status

Published

Research group

  • CNS Gene Therapy

ISBN/ISSN/Other

  • ISSN: 1090-2422