Role of Src in signal transduction pathways
Role of Src in signal transduction pathways
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DOI：
10.1042/bst0300011
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发表时间：
2002-04-01
影响因子：
3.9
通讯作者：
Courtneidge, SA
中科院分区：
文献类型：
--
作者：
Courtneidge, SA
SRC是第一个被发现的癌基因，也是第一个蛋白酪氨酸激酶。对Src如何转化细胞的研究一直是一个丰富的领域，它导致了对细胞周期的控制、细胞骨架的组织以及生长因子非依赖性生长的深入了解。然而，我们仍然不完全了解Src到底是做什么的。在正常细胞中，Src参与了细胞分裂的调控、自分泌生长因子的产生、细胞的生存反应以及细胞的运动。我的实验室一直专注于Src和相关的激酶在细胞对有丝分裂生长因子的反应中的参与。我们已经证明，当有丝分裂原如血小板衍生生长因子处理细胞时，Src激酶的活性是细胞进入细胞周期所必需的。SRC活性启动了一系列信号转导，涉及到适配蛋白Shc，最终导致转录因子Myc的转录激活。此外，我们还表明，在缺乏抑癌基因p53的细胞中，对Src的这一要求被取消，这表明在正常细胞中，Src的另一个功能是抑制p53的作用。
Src was the first oncogene to be discovered, and the first protein tyrosine kinase. The study of how Src transforms cells has been a rich field that has lead to insights into the control of the cell cycle, the organization of the cytoskeleton, and growth factor-independent growth. Yet we still do not fully understand exactly what Src does. In normal cells, Src has been implicated in the control of cell division, the production of autocrine growth factors, the cell's survival response, as well as in cell motility. My laboratory has focused on the involvement of Src and related kinases in the response of cells to mitogenic growth factors. We have shown that the activity of Src kinases is necessary for cells to enter the cell cycle when treated with mitogens such as platelet-derived growth factor. Src activity initiates a signal transduction cascade, involving the adaptor protein Shc, which culminates in the transcriptional activation of the transcription factor Myc. Furthermore we have also shown that this requirement for Src is abrogated in cells lacking the tumour suppressor p53, suggesting that another of Src's functions in normal cells is to suppress the actions of p53.