The role of PIPP in cell polarization and proliferation.

正常情况下，细胞只有在受到激素或生长因子等刺激时才会分裂。当受到刺激时，细胞内会产生一系列信号，导致细胞分裂和发育。对生长因子刺激作出反应的信号通路之一是PI3-激酶通路。这一途径与许多不同的人类癌症有关，当细胞无法控制地分裂并侵入周围组织时就会发生这种癌症。在生长因子刺激下，PI3-激酶产生一种称为PtdIns(3，4，5)P3的分子，导致信号通路中许多蛋白质的激活。所有含有PI3-Kinase的细胞也都有酶，这些酶可以关闭PI3-Kinase产生的信号，因此可能在预防癌症和调节细胞发育方面发挥作用。我们已经确定了一种名为PIPP的新酶，并表明它可以关闭PI3-激酶产生的信号。我们计划通过增加或减少细胞中PIPP的数量并分析其对细胞生长发育的影响来研究PIPP的作用。我们还鉴定了一些与PIPP结合的蛋白质，我们将研究这些蛋白质在调节细胞信号中所起的作用。此外，我们计划通过产生缺乏PIPP(基因敲除小鼠)的小鼠，并评估其对发育和癌症的影响，来表征PIPP在整个动物中的功能。

Normally cells only divide when they receive a stimulus such as from a hormone or growth factor. Upon stimulation, a series of signals are generated inside the cell which lead to cell division and development. One of the signaling pathways which responds to growth factor stimulation is the PI3-kinase pathway. This pathway has been implicated in many different human cancers which occur when cells divide uncontrollably and invade into the surrounding tissues. Following growth factor stimulation, PI3-kinase generates a molecule known as PtdIns(3,4,5)P3 which leads to the activation of many proteins in the signaling pathway. All cells which have PI3-kinase also have enzymes which act to switch off the signals generated by PI3-kinase and thus may play a role in preventing cancer and regulating cell development. We have identified a new enzyme known as PIPP and have shown that it acts to switch off the signals generated by PI3-kinase. We plan to investigate the role of PIPP by increasing or decreasing the amount of PIPP in cells and analysing the effects on cell growth and development. We have also identified a number of proteins which bind to PIPP and we will investigate the role these proteins play in regulating cell signaling. In addition, we plan to characterize the function of PIPP in a whole animal by generating mice which lack PIPP (knockout mice) and assessing the effects on development and cancer.