BIOCHEMICAL GENETIC STUDIES OF CELL SURVIVAL PATHWAYS

描述（根据研究者摘要逐字附上）：正常 多细胞生物的发展依赖于细胞间的平衡 增殖、分化和程序性细胞死亡（PCD）。许多类型的 包括癌症在内的人类疾病似乎与异常 调节PCD和增殖。尽管有大量的信息， 生存和抗PCD的信号通路仍然很差 明白我们已经开始利用Akt信号研究细胞存活途径 作为一个模型系统。以前对阿基的研究主要依赖于建立细胞 线因此，关于Akt和Akt的体内功能知之甚少。 在原代细胞中介导Akt抗凋亡活性的信号传导途径。 我们使用嵌合体小鼠的初步研究表明，Akt在小鼠体内起着重要的作用。 在造血细胞存活和发育中的重要作用。我们还 使用肽文库鉴定了Akt的几种潜在的体内靶点， 基因筛查方法本建议的总体目标是 了解Akt信号通路的结构和 Akt在抗凋亡信号转导中的作用及其发展。具体目标是 建议是：1。使用免疫组织化学方法研究Akt在造血存活中的作用 原代细胞和嵌合体小鼠中。2.阐明了 Akt介导细胞存活。

DESCRIPTION (appended verbatim from investigator's abstract): Normal development of multicellular organisms relies on the balance between cell proliferation, differentiation, and programmed cell death (PCD). Many types of human diseases including cancer appear to be associated with aberrant regulation of PCD and proliferation. Despite the wealth of information, mammalian-signaling pathways for survival and anti-PCD remain poorly understood. We have begun to study cell survival pathways using Akt signaling as a model system. Previous studies of Aki mostly relied on established cell lines. Hence, very little is known about the in vivo function of Akt and signaling pathways that mediate Akt anti-apoptosis activity in primary cells. Our preliminary studies using chimeric mice indicated that Akt plays an important role in hematopoietic cell survival and development. We have also identified several potential in vivo targets of Akt using peptide libraries and genetic screen approaches. The overall objective of this proposal is to understand the architecture of the Akt signaling pathway and the function of Akt in anti-apoptosis signaling and development. The specific aims of this proposal are to: 1. Investigate the role of Akt in hematopoietic survival using primary cells and in chimera mice. 2. Elucidate the molecular mechanisms of how Akt mediates cell survival.