ACTIVATION OF RAS AND PROTECTION FROM APOPTOTIC CELL-DEATH BY BDNF INPC12 CELLS EXPRESSING TRKB

A clonal deoxyribonucleic acid (cDNA) clone of mouse trkB was expresse d in cells of the rat PC12 pheochromocytoma cell line. The transforman ts followed apoptotic death upon serum deprivation. The addition of br ain-derived neurotrophic factor (BDNF) to the culture medium supported the survival and neurite extension of the transformants in a serum-fr ee condition. A Trk-family-specific protein kinase inhibitor, K-252a, inhibited the survival and neurite extension of the transformants in t he presence oi BDNF. BDNF activated autophosphorylation of trkB and ca used the accumulation of a guanosine triphosphate (GTP)-bound. form of Ras, both of which effects were also inhibited by K-252a. These resul ts suggested that BDNF-triggered Ras activation is important for the s urvival and neuronal differentiation of PC12 cells in a serum-free con dition.