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蛋白激酶B/蛋白激酶Akt:细胞增殖、存活及胰岛素反应的关键调节因子?

PKB/Akt: a key mediator of cell proliferation, survival and insulin responses?

作者信息

Lawlor M A, Alessi D R

机构信息

MRC Protein Phosphorylation Unit, Department of Life Sciences, University of Dundee, UK.

出版信息

J Cell Sci. 2001 Aug;114(Pt 16):2903-10. doi: 10.1242/jcs.114.16.2903.

Abstract

The serine/threonine protein kinase PKB (also known as Akt) is thought to be a key mediator of signal transduction processes. The identification of PKB substrates and the role PKB phosphorylation plays in regulating these molecules have been a major focus of research in recent years. A recently developed motif-profile scoring algorithm that can be used to scan the genome for potential PKB substrates is therefore a useful tool, although additional considerations, such as the evolutionary conservation of the phosphorylation site, must also be taken into account. Recent evidence indicates that PKB plays a key role in cancer progression by stimulating cell proliferation and inhibiting apoptosis and is also probably a key mediator of insulin signalling. These findings indicate that PKB is likely to be a hot drug target for the treatment of cancer, diabetes and stroke. There are, however, a number of pitfalls of methodologies currently employed to study PKB function, and therefore caution should be used in interpretation of such experiments.

摘要

丝氨酸/苏氨酸蛋白激酶PKB(也称为Akt)被认为是信号转导过程的关键介质。近年来,确定PKB底物以及PKB磷酸化在调节这些分子中所起的作用一直是研究的主要重点。因此,最近开发的一种基序谱评分算法可用于扫描基因组以寻找潜在的PKB底物,它是一种有用的工具,不过还必须考虑其他因素,例如磷酸化位点的进化保守性。最近的证据表明,PKB通过刺激细胞增殖和抑制细胞凋亡在癌症进展中起关键作用,并且可能也是胰岛素信号传导的关键介质。这些发现表明,PKB可能是治疗癌症、糖尿病和中风的热门药物靶点。然而,目前用于研究PKB功能的方法存在许多缺陷,因此在解释此类实验时应谨慎。

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