Sustained phosphorylation of mitogen-activated protein kinase is required for basic fibroblast growth factor-mediated axonal branch formation in cultured rat hippocampal neurons
K. Abe et al., Sustained phosphorylation of mitogen-activated protein kinase is required for basic fibroblast growth factor-mediated axonal branch formation in cultured rat hippocampal neurons, NEUROCHEM I, 38(4), 2001, pp. 309-315
Basic fibroblast growth factor (bFGF) has been reported to promote the form
ation of axonal branches in cultured brain neurons. In the present study, w
e investigated whether the mitogen-activated protein kinase (MAPK) cascade
was involved in this action of bFGF in cultured rat hippocampal neurons. Re
combinant human bFGF (0.1-10 ng/ml) induced phosphorylation of p44/42 MAPK
in a concentration and time-dependent manner. The phosphorylation of p44/42
MAPK occurred rapidly within 5 min after addition of bFGF, and lasted for
48 h. The bFGF-induced phosphorylation of p44/42 MAPK and axonal branch for
mation were both blocked by simultaneous addition of U0126 and PD98059, spe
cific inhibitors of MAPK kinases. Furthermore, when U0126 and PD98059 were
added 24 h after bFGF, phosphorylation of p44/42 m MAPK was decreased, and
axonal branch formation was stopped. These results suggest that sustained a
ctivation of the MAPK cascade is required for bFGF-mediated axonal branch f
ormation. (C) 2001 Elsevier Science Ltd. All rights reserved.