Among the 3 mitogen-activated protein kinases--ERK, p38 MAPK and JNK--JNK has been suggested to participate in apoptosis, whereas p38 MAPK is thought to be part of the differentiation response. There are many common inducers of JNK and p38 MAPK, but the mechanisms underlying the differential response to apoptosis and differentiation are poorly understood. We found that heatshock activated p38 MAPK at 3 min after exposure to a temperature of 44 degrees C in stress-hypersensitive PC12m3 mutant cells, while it activated JNK at 20 min after the same heat treatment. However, heatshock activated p38 MAPK 5min after heat treatment and JNK 10 min after heat treatment in PC12 parental cells. The extent of phosphorylation of p38 MAPK induced by heat shock in PC12m3 cells was significantly greater than that in PC12 parental cells, and a high level of heat-shock-induced neurite outgrowth was observed only in PC12m3 cells. On the other hand, heat-shock-induced JNK activation appeared more quickly and apoptosis started earlier in PC12 parental cells. These findings indicate that short stress induces p38 MAPK and longer stress induces JNK, and that the response of these kinases to heat shock differs depending on cell type.