MECHANISM OF SERINE/THREONINE KINASE SURVIVAL PROMOTION

血清和某些生长因子促进存活并抑制凋亡， 但实现这一点的机制尚不清楚。 活化形式 Ras、Raf和Src正在转变，但不能提供生存 血清戒断后信号，而抑制PI 3激酶 加速的细胞凋亡和S/T激酶Akt的活化形式， PI 3 K的下游效应子，阻断凋亡。 Akt的能力， 促进存活依赖于其激酶活性。 pi 3 k和Akt 似乎是一个转导生存信号的途径的组成部分 其最终阻断Ced 3/ICE蛋白酶活性。 这项建议 重点描述Akt促进生存的机制 集中在三个方面。(1)Akt会传递生存信号吗 通过使蛋白质翻译的阻遏物4 E-BP 1失活，(2)并 Akt在Bcl-2家族水平干预凋亡级联反应 成员，线粒体的完整性，caspase活性或Ced-4/Apaf-1？ (3)Akt是否通过增加细胞-细胞粘附和/或 细胞内水平的b-连环蛋白通过抑制GSK 3？

Serum and certain growth factors promote survival and inhibit apoptosis, but the mechanism by which this is achieved is unclear. Activated forms of Ras, Raf and Src are transforming but do not deliver a survival signal upon serum withdrawal, whereas inhibition of PI3kinase accelerated apoptosis and an activated form of the S/T kinase Akt, a downstream effector of PI3K, blocked apoptosis. The ability of Akt to promote survival was dependent upon its kinase activity. PI3K and Akt appear to be components of a pathway that transduces a survival signal that ultimately blocks Ced3/ICE protease activity. This proposal focusses on delineating the mechanism(s) by which Akt promotes survival concentrating on three aspects. (1) Does Akt deliver a survival signal by inactivating 4E-BP1, the repressor of protein translation? (2) Does Akt intervene in the apoptosis cascade at the level of Bcl-2 family members, integrity of mitochondria, caspase activity or Ced-4/Apaf-1? (3) Does Akt promote survival by increasing cell-cell adhesion and/or intracellular levels of b-catenin via inhibition of GSK3?