The PI 3-kinase/Akt signaling pathway plays a crucial role in delivering an anti-apoptotic signal to cells. The study investigated the mechanisms by which growth factors induce survival and inhibit apoptosis. Activated Ras, Raf, and Src, despite their transforming properties, were insufficient to block apoptosis upon serum withdrawal. In contrast, inhibition of PI 3-kinase accelerated apoptosis, while activation of Akt, a downstream effector of PI 3-kinase, blocked apoptosis. The ability of Akt to promote survival was dependent on its kinase activity and was proportional to its activity. In Rat1a fibroblasts, activated Akt did not alter Bcl-2 or Bcl-XL expression but inhibited Ced3/ICE-like activity, suggesting that the PI 3-kinase/Akt pathway inhibits apoptosis by blocking Ced3/ICE-like proteases. These findings indicate that the PI 3-kinase/Akt pathway transduces a survival signal that blocks apoptosis, and that the ability of Akt to deliver this signal is dependent on its kinase activity. The study also explored potential mechanisms by which Akt promotes survival, including modulation of Bcl-2 family members and inhibition of Ced3/ICE-like proteases. The results suggest that the PI 3-kinase/Akt pathway may have broader roles in embryonic development and adult tissue longevity.The PI 3-kinase/Akt signaling pathway plays a crucial role in delivering an anti-apoptotic signal to cells. The study investigated the mechanisms by which growth factors induce survival and inhibit apoptosis. Activated Ras, Raf, and Src, despite their transforming properties, were insufficient to block apoptosis upon serum withdrawal. In contrast, inhibition of PI 3-kinase accelerated apoptosis, while activation of Akt, a downstream effector of PI 3-kinase, blocked apoptosis. The ability of Akt to promote survival was dependent on its kinase activity and was proportional to its activity. In Rat1a fibroblasts, activated Akt did not alter Bcl-2 or Bcl-XL expression but inhibited Ced3/ICE-like activity, suggesting that the PI 3-kinase/Akt pathway inhibits apoptosis by blocking Ced3/ICE-like proteases. These findings indicate that the PI 3-kinase/Akt pathway transduces a survival signal that blocks apoptosis, and that the ability of Akt to deliver this signal is dependent on its kinase activity. The study also explored potential mechanisms by which Akt promotes survival, including modulation of Bcl-2 family members and inhibition of Ced3/ICE-like proteases. The results suggest that the PI 3-kinase/Akt pathway may have broader roles in embryonic development and adult tissue longevity.