EGF-Induced sustained tyrosine phosphorylation and decreased rate of down-regulation of EGF receptor in PC12h-R cells which show neuronal differentiation in response to EGF |
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Authors: | Masashi Yamada Toshihiko Ikeuchi Saburo Aimoto Dr Hiroshi Hatanaka |
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Institution: | (1) Research Center for Protein Engineering, Institute for Protein Research, Osaka University, 565 Suita, Osaka, Japan;(2) Japan Society for the Promotion of Science, Japan;(3) Division of Protein Biosynthesis, Institute for Protein Research, Osaka University, 3-2 Yamadaoka, 565 Suita, Osaka, Japan |
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Abstract: | PC12h-R cell, a subclone of PC12 cells, exhibited a neuron-like phenotype, including neurite outgrowth and increased acetylcholinesterase
activity, in response to epidermal growth factor (EGF) as well as nerve growth factor (NGF). We examined the mechanism by
which EGF induced the neuronal differentiation in PC12h-R cells. The EGF-induced neuronal differentiation of PC12h-R cells
was not blocked by K252a, whereas that induced by NGF was. EGF induced sustained tyrosine phosphorylation of the EGF receptor
in PC12h-R cells, but not in the parent PC12h cells, which do not show neuronal differentiation in response to EGF. In addition,
the rate of EGF-induced down-regulation of the EGF receptor in PC12h-R cells was decreased compared with that in PC12h cells.
Furthermore, we found that the duration of EGF-induced tyrosine phosphorylation of the EGF receptor in PC12h-R cells was similar
to that of NGF-induced tyrosine phosphorylation of p140
trkA in PC12h cells. The EGF-induced phosphorylation of the EGF receptor in PC12h cells was less sustained than that of p140
trkA by NGF in PC12h cells. These findings suggested that the EGF-induced neuronal differentiation of PC12h-R cells is due to
the sustained activation of the EGF receptor, resulting from the decreased down-regulation of the EGF receptor and that the
duration of the receptor tyrosine kinase activity determines the cellular responses of PC12 cells. We concluded that sustained
activation of the receptor tyrosine kinase induces neuronal differentiation, although transient activation promotes proliferation
of PC12 cells.
Special issue dedicated to Dr. Hans Thoenen. |
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Keywords: | Neurotrophic factor Trk NGF tyrosine kinase PC12 cell |
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