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.
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/Ca(2+) 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.
Chou
Alice H
AH
Department of Biological Chemistry, School of Medicine, University of California, Los Angeles, California, CA 90095, USA.
Howard
Bruce D
BD
D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects* / Q000235:genetics; D004336:Drug Antagonism; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D007211:Indoles / Q000494:pharmacology*; D008301:Maleimides / Q000494:pharmacology*; D020932:Nerve Growth Factor / Q000494:pharmacology*; D016716:PC12 Cells; D014176:Protein Biosynthesis; D011493:Protein Kinase C / Q000037:antagonists & inhibitors; D011506:Proteins / Q000235:genetics; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis* / Q000235:genetics; D051381:Rats; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics; D051153:Wnt Proteins; D051155:Wnt1 Protein; D060508:Wnt3 Protein; D029961:Zebrafish Proteins
D004791:Enzyme Inhibitors; D007211:Indoles; D008301:Maleimides; D011506:Proteins; D011518:Proto-Oncogene Proteins; D051153:Wnt Proteins; D051155:Wnt1 Protein; C495245:Wnt1 protein, rat; D060508:Wnt3 Protein; D029961:Zebrafish Proteins; D020932:Nerve Growth Factor; D011493:Protein Kinase C; C070515:bisindolylmaleimide I