p21(ras) stimulates pathways in addition to ERK, p38, and Akt to induce elongation of neurites in PC12 cells

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.