THE WNT-1 PROTOONCOGENE REGULATES MAP KINASE ACTIVATION BY MULTIPLE GROWTH-FACTORS IN PC12 CELLS

PC12/Wnt-1 cells display morphological changes in response to stimulat ion by select growth factors but do not respond to NGF. Furthermore, s timulation by EGF can induce neuronal differentiation in these cells b ut not in wild type cells. We have found that in these cells, compared to wild type PC12 cells, FGF and EGF stimulation of MAP kinase activi ty is enhanced, while NGF stimulation of MAP kinase in diminished, Fin ally, in cells expressing Wnt-1, the effect of cyclic adenosine monoph osphate (cAMP) on MAP kinase activation is reversed; cAMP stimulates M AP kinase in wild type PC12 cells but inhibits MAP kinase in PC12/Wnt- 1 cells. These data suggest that Wnt-1 expression alters the specifici ty of growth factor signaling in neuronal cells.