Sa. Burchill et al., ACTIVATION OF P21(RAS) BY NERVE GROWTH-FACTOR IN NEUROBLASTOMA-CELLS, Journal of the neurological sciences, 133(1-2), 1995, pp. 3-10
Nerve growth factor (NGF) is essential for the differentiation and sur
vival of sympathetic and sensory neurones and is thought to play a rol
e in the differentiation of neuroblastoma. In this study we have shown
NGF decreased the mRNA level of the two GTPase activating proteins ne
urofibromin (containing the NF1-GRD) and type 1 GAP(120) in two neurob
lastoma cell lines, IMR-32 and SK-N-SH. This effect was seen within 15
min exposure to NGF and was maintained up to 2 h after the addition o
f NGF. Treatment with NGF increased the amount of GTP bound p21(ras) 3
-fold, within 20 min exposure. Western blot analysis showed SK-N-SH an
d IMR-32 cells to contain equal amounts of p21(ras) protein and these
levels were unchanged by NGF treatment. However, NGF induced an increa
se in the level of neurofilament L protein, which was accompanied by a
n increase in neurite extension. These effects of NGF occurred in the
absence of growth inhibition. In conclusion, our results demonstrate a
decrease in GTPase activating proteins and activation of p21(ras) by
NGF in IMR-32 and SK-N-SH cells, thus implicating p21(ras) in NGF sign
al transduction in neuroblastoma.