BIOCHEMICAL GENETIC STUDIES OF CELL SURVIVAL PATHWAYS

描述(逐字摘自调查人员摘要)：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有关 PCD与细胞增殖的调控。尽管有丰富的信息， 哺乳动物生存和抗PCD的信号通路仍然很差 明白了。我们已经开始研究使用Akt信号的细胞生存途径 作为一个模范系统。以往对Aki的研究大多依赖于已建立的细胞 台词。因此，对Akt和Akt在体内的功能知之甚少。 在原代细胞中介导Akt抗凋亡活性的信号通路。 我们用嵌合小鼠进行的初步研究表明，Akt扮演着一种 在造血细胞的生存和发育中发挥重要作用。我们还有 利用多肽文库和 基因筛查即将到来。这项提议的总体目标是 了解Akt信号通路的结构和Akt信号通路的功能 AKT在抗细胞凋亡信号转导和发展中的作用。这样做的具体目的是 建议：1.研究Akt在造血存活中的作用 原代细胞和嵌合体小鼠。2.阐明其分子机制 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.