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PC12h‐R cell, a subclone of PC12 cells, shows EGF‐induced neuronal differentiation and sustained signaling
Author(s) -
Yamada M.,
Ikeuchi T.,
Aimoto S.,
Hatanaka H.
Publication year - 1996
Publication title -
journal of neuroscience research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.72
H-Index - 160
eISSN - 1097-4547
pISSN - 0360-4012
DOI - 10.1002/(sici)1097-4547(19960201)43:3<355::aid-jnr10>3.0.co;2-4
Subject(s) - epidermal growth factor , neurite , nerve growth factor , microbiology and biotechnology , tyrosine phosphorylation , cellular differentiation , endocrinology , medicine , signal transduction , biology , tyrosine kinase , chemistry , receptor , biochemistry , in vitro , gene
Unlike nerve growth factor (NGF), epidermal growth factor (EGF) does not induce neuronal differentiation but promotes proliferation of the rat pheochromocytoma PC12 cells. We found that PC12h‐R, a subclone of PC12 cells, differentiated into neuron‐like cells in response to EGF as well as to NGF. PC12h‐R cells treated with EGF extended neurites, attenuated cell proliferation, and increased the levels of tyrosine hydroxylase protein synthesis and of acetylcholinesterase activity as those treated with NGF. The EGF‐induced differentiation of PC12h‐R cells was not mediated by the indirect activation of p140 trk A by EGF. In addition, EGF induced the sustained tyrosine phosphorylation of the EGF receptor, mitogen‐activated protein (MAP) kinases, and 46 and 52 kDa proteins, and the prolonged activation of MAP kinases in PC12h‐R cells compared with the parent PC12h, which does not show EGF‐induced differentiation. The response of PC12h‐R cells to EGF was not simply due to an increase in the level of EGF receptor protein. These results indicated that the duration of EGF‐induced signaling might determine the cellular response of PC12 cells between cell proliferation and neuronal differentiation. © 1996 Wiley‐Liss, Inc.