MECHANISM OF SERINE/THREONINE KINASE SURVIVAL PROMOTION

血清和某些生长因子促进存活和抑制细胞凋亡， 但实现这一目标的机制尚不清楚。已激活的表单 RAS、RAF和Src正在转型，但不能提供生存 在血清停用时发出信号，而抑制PI3激酶 促细胞凋亡与S/T蛋白激酶AKT的活化形式 PI3K下游效应分子阻断细胞凋亡。Akt的能力 促进存活依赖于其激酶活性。PI3K和Akt 似乎是传递生存信号的途径的组成部分 这最终会阻止Ced3/ICE的蛋白酶活性。这项建议 重点描述Akt促进生存的机制(S) 集中在三个方面。(1)Akt是否传递了生存信号 通过使4E-BP1失活，蛋白质翻译的抑制因子？(2) AKT在Bcl2家族水平上干预细胞调亡 成员，线粒体的完整性、caspase活性还是Ced-4/APAF-1？ (3)Akt是否通过增加细胞间黏附和/或 抑制GSK3？细胞内b-连环蛋白的水平？

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?