Activation of Ras and protection from apoptotic cell death by BDNF in PC12 cells expressing TrkB.

A clonal deoxyribonucleic acid (cDNA) clone of mouse trkB was expressed in cells of the rat PC12 pheochromocytoma cell line. The transformants followed apoptotic death upon serum deprivation. The addition of brain-derived neurotrophic factor (BDNF) to the culture medium supported the survival and neurite extension of the transformants in a serum-free condition. A Trk-family-specific protein kinase inhibitor, K-252a, inhibited the survival and neurite extension of the transformants in the presence of BDNF. BDNF activated autophosphorylation of trkB and caused the accumulation of a guanosine triphosphate (GTP)-bound form of Ras, both of which effects were also inhibited by K-252a. These results suggested that BDNF-triggered Ras activation is important for the survival and neuronal differentiation of PC12 cells in a serum-free condition.