The Wnt-1 proto-oncogene regulates MAP kinase activation by multiple growth factors in PC12 cells.
PC12/Wnt-1 cells display morphological changes in response to stimulation by select growth factors but do not respond to NGF. Furthermore, stimulation by EGF can induce neuronal differentiation in these cells but 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 activity is enhanced, while NGF stimulation of MAP kinase in diminished. Finally, in cells expressing Wnt-1, the effect of cyclic adenosine monophosphate (cAMP) on MAP kinase activation is reversed; cAMP stimulates MAP kinase in wild type PC12 cells but inhibits MAP kinase in PC12/Wnt-1 cells. These data suggest that Wnt-1 expression alters the specificity of growth factor signaling in neuronal cells.
D000818:Animals; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism*; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology; D000242:Cyclic AMP / Q000502:physiology; D004789:Enzyme Activation / Q000235:genetics; D004815:Epidermal Growth Factor / Q000494:pharmacology; D066246:ErbB Receptors / Q000378:metabolism; D005346:Fibroblast Growth Factors / Q000494:pharmacology; D015972:Gene Expression Regulation, Neoplastic; D006133:Growth Substances / Q000494:pharmacology*; D019278:Matrix Metalloproteinase 3; D008666:Metalloendopeptidases / Q000235:genetics; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases; D009414:Nerve Growth Factors / Q000494:pharmacology; D016716:PC12 Cells; D017346:Protein Serine-Threonine Kinases / Q000096:biosynthesis; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis / Q000502:physiology*; D019908:Proto-Oncogene Proteins c-raf; D011519:Proto-Oncogenes; D051381:Rats; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*; D013268:Stimulation, Chemical; D051153:Wnt Proteins; D051155:Wnt1 Protein; D029961:Zebrafish Proteins
D006133:Growth Substances; D009414:Nerve Growth Factors; D011518:Proto-Oncogene Proteins; D051153:Wnt Proteins; D051155:Wnt1 Protein; C495245:Wnt1 protein, rat; D029961:Zebrafish Proteins; D005346:Fibroblast Growth Factors; D004815:Epidermal Growth Factor; D000242:Cyclic AMP; D066246:ErbB Receptors; D017346:Protein Serine-Threonine Kinases; D019908:Proto-Oncogene Proteins c-raf; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases; D008666:Metalloendopeptidases; D019278:Matrix Metalloproteinase 3