Activation of microtubule-associated protein kinase in PC12D cells in response to both fibroblast growth factor and epidermal growth factor and concomitant stimulation of the outgrowth of neurites.
When PC12D cells, a subline of PC12 cells, were cultured with nerve growth factor (NGF), outgrowth of neurites was promoted even when RNA synthesis was blocked. This property of PC12D cells may enable us to resolve the mechanism of the outgrowth of neurites that is induced in a transcription-independent manner. The outgrowth of neurites from PC12D cells was also stimulated in response to fibroblast growth factor (FGF) and was slightly stimulated in response to epidermal growth factor (EGF). The brief exposure of intact PC12D cells not only to NGF but also to FGF or to EGF stimulated a protein kinase activity in extracts of such cells that catalyzed phosphorylation of microtubule-associated protein 1 (MAP-1) and MAP-2 in vitro. Similar dose-response relationships for the effects of NGF and of FGF on the activation of the kinase and on the outgrowth of neurites were observed. The effects of combinations of NGF and GFG or EGF were not additive in terms of either the outgrowth of neurites or the increase in the kinase activity. Treatment of cells with phorbol 12-myristate 13-acetate (PMA) also stimulated the kinase activity that phosphorylated MAPs in vitro. However, the level of the enzymatic activity that resulted from the combined treatment of cells with PMA and NGF was additive, as is the case with dibutyryl cyclic AMP and NGF. These findings suggest that NGF, FGF, and EGF may stimulate the activity of the same MAP kinase.(ABSTRACT TRUNCATED AT 250 WORDS)
Sano
M
M
Institute for Developmental Research, Aichi Prefectural Colony, Japan.
Kitajima
S
S
D000818:Animals; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D003907:Dexamethasone / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation; D004815:Epidermal Growth Factor / Q000494:pharmacology*; D005346:Fibroblast Growth Factors / Q000494:pharmacology*; D016501:Neurites / Q000502:physiology*; D016716:PC12 Cells / Q000378:metabolism*; D011494:Protein Kinases / Q000378:metabolism*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D005346:Fibroblast Growth Factors; D004815:Epidermal Growth Factor; D003907:Dexamethasone; D011494:Protein Kinases; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D013755:Tetradecanoylphorbol Acetate