FIG. 11.

Participation of Hsp72 and heat shock-activated kinases in caspase-independent cell death of fibroblasts. Heat shock causes rapid activation of JNK, ERK, Akt, and p38 kinases and slow induction of Hsp72. JNK activation leads to cell death, while ERK and Akt activation enhances survival. Hsp72 can prevent cell death via suppression of JNK but not through activation of ERK or Akt. Prevention of Hsp72 accumulation by antisense-RNA expression (AS RNA) eliminates the inhibitory effect of mild heat shock on JNK activity and abolishes thermotolerance. PD, PD98059; WM, wortmannin; SB, SB203580.