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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
Author(s) -
Sano Mamoru,
Kitajima Satoko
Publication year - 1992
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.1992.tb09333.x
Subject(s) - neurite , nerve growth factor , epidermal growth factor , biology , fibroblast growth factor , microbiology and biotechnology , protein kinase c , protein kinase a , medicine , endocrinology , phosphorylation , in vitro , cell culture , biochemistry , receptor , genetics
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 FGF 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. The close relationship between the activation of the kinase and the outgrowth of neurites from PC12D cells in response to various agents suggests that activation of the kinase may play an important role in the outgrowth of neurites.