Fig. 3. Roles for ERK activation in resistance to stress-induced apoptosis. Concomitantly with the activation of the Akt pathway (see Fig. 1), integrin ligation leads to the activation of the Ras-Raf-MEK-ERK cascade. Activated Ras recruits Raf, which binds to and activates MEK, and subsequently ERK, which are all bound on a ksr scaffold. The phosphorylation of Bcl-2 by Erk on Thr 56, Thr 74 or Ser 84 prevents its recognition by ubiquitin ligases, whereas phosphorylation at Ser 70 has been reported to both increase and decrease the prosurvival character of Bcl-2. Of the ksr-bound proteins, both Raf and Mek (as well as the Erk-substrate, Rsk, not shown) are capable of phosphorylating the proapoptotic protein Bad (indicated by the green circling arrow, starred), leading to its displacement from the mitochondria and subsequent sequestration by 14-3-3 proteins.