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Inhibition by Wnt-1 or Wnt-3a of nerve growth factor-induced differentiation of PC12 cells is reversed by bisindolylmaleimide-I but not by several other PKC inhibitors

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Abstract

Wnt-1 and Wnt-3a exhibit redundancy in neural crest development. We have found that they do not produce the same effects on PC12 cells, which were obtained from the adrenal medulla, a neural crest derivative. However, both Wnt-1 or Wnt-3a inhibit nerve growth factor (NGF)-induced neurite outgrowth. The inhibition is reversed by the protein kinase C (PKC) inhibitor, bisindolylmaleimide-I, but it did not reverse Wnt-1-induced activation of the canonical Wnt pathway. The Wnt-1 inhibitory effect was not reversed by several other PKC inhibitors, by phorbol ester-induced down-regulation of PKC, or by pertussis toxin, which is known to inhibit another Wnt signaling pathway, the Wnt/Ca2+ pathway. We suggest that bisindolylmaleimide-I acts by affecting either a pathway downstream from Lef-1/Tcf in the canonical pathway or a Wnt signaling pathway other than the canonical pathway. In either case, the bisindolylmaleimide-I sensitivity of this pathway should aid in its identification.

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  1. Alice H Chou

    Present address: Department of Molecular, Cell and Developmental Biology, University of California, Los Angeles, California, USA

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  1. Department of Biological Chemistry, School of Medicine, University of California, Los Angeles, 90095, California, CA, USA

    Alice H Chou & Bruce D Howard

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  1. Alice H Chou
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  2. Bruce D Howard
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Correspondence to Bruce D Howard.

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Chou, A., Howard, B. Inhibition by Wnt-1 or Wnt-3a of nerve growth factor-induced differentiation of PC12 cells is reversed by bisindolylmaleimide-I but not by several other PKC inhibitors. Oncogene 21, 6348–6355 (2002). https://doi.org/10.1038/sj.onc.1205791

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  • DOI: https://doi.org/10.1038/sj.onc.1205791

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