Rw. Burry, p21(ras) stimulates pathways in addition to ERK, p38, and Akt to induce elongation of neurites in PC12 cells, J NEUROSC R, 63(1), 2001, pp. 45-53
Initiation and elongation of neurities in PC12 cells has been shown to be s
timulated by nerve growth factor (NGF). Initiation of NGF-stimulated neurit
es in a PC12 subclone (PC12-N09) is rapid, giving rise to short neurites th
at do not elongate after 1 day. To determine whether increasing activation
of p21(ras) could restore neurite elongation in these cells and whether it
would affect the phosphorylation of signaling proteins, the subclone PC12-N
09 was transfected with constitutively active p21(ras61L) (PC12-N09ras61L)
and neurite outgrowth with or without NGF was determined. Overexpression of
wild-type p21(ras) (PC12-N09rasWT) did not lead to spontaneous neurite ini
tiation but restored the ability of NGF to stimulate continuous neurite elo
ngation. However, NGF-stimulated phosphorylation of ERK, p38, and Akt in PC
12-N09rasWT cells is similar in duration to that in PC12-N09 cells, indicat
ing that the p21(ras) signaling through ERK, p38, and AM was not involved i
n the restoration of normal neurite elongation in PC12-N09 cells. These res
ults show that p21(ras)-activated pathways other than ERK, p38, and Akt are
necessary for appropriate NGF-stimulated neurite elongation in PC12 cells.
(C) 2001 Wiley-Liss, Inc.