Nerve growth factor induces proliferation of PC12 cells through Cdc42

Nerve growth factor (NGF) can change neurite outgrowth and cellular morphology of rat adrenal pheochromocytoma PC12 cells. In the present study, stable PC12 cells with constitutively active form (L61Cdc42), the dominant negative constructs (N17Cdc42), and wild type Cdc42 did not proliferate in low serum condition. However, on exposure to NGF, PC12 cells transfected with L61Cdc42 cDNA proliferated, whereas wild type Cdc42 and N17Cdc42 cDNA-transfected PC12 cells did not. When the cells were stimulated with NGF, ERK1/2 was transiently activated in L61Cdc42-transfected PC12 cells, whereas the activation of ERK1/2 was sustained in other cell lines. NGF repressed the induction of p21WAF1, cyclin-dependent kinase (CDK) inhibitor, in L61Cdc42 transfected PC12 cells, whereas NGF induced the expression of p21WAF1 in other PC12 cell lines.