ACTIVATION OF MITOGEN-ACTIVATED PROTEIN-KINASE AND P70S6 KINASE IS NOT CORRELATED WITH CEREBELLAR GRANULE CELL-SURVIVAL

We have investigated the role of mitogen-activated protein (MAP) kinas e in the survival of cerebellar granule cells in primary culture, Brai n-derived neurotrophic factor (BDNF) and insulin, but not epidermal gr owth factor (EGF), promoted the survival of P-6 cerebellar granule neu rons, BDNF promoted a sustained activation of MAP kinase, whereas that induced by EGF was only transient, Insulin promoted a small but trans ient activation of MAP kinase that was completely blocked by PD98059, an inhibitor of MAP kinase kinase activation, PD98059 had no effect on the insulin- or BDNF-induced survival of cerebellar granule cells, We also investigated the role of p70S6 kinase in survival. The activatio n of p70S6 kinase by EGF was transient, whereas BDNF and insulin promo ted a sustained activation of p70S6 kinase. Rapamycin, which blocked p 70S6 kinase activation, had no effect on the BDNF- or insulin-induced survival of cerebellar granule cells. We conclude that sustained activ ation of MAP kinase is not correlated with the survival response of ce rebellar granule cells; indeed insulin-mediated survival is independen t of MAP kinase. Survival of cerebellar granule cells is also independ ent of the activation of p70S6 kinase.