The role of PIPP in cell polarization and proliferation.

PIPP 在细胞极化和增殖中的作用。

• 批准号: nhmrc : 436638
• 负责人: Prof Christina Mitchell
• 金额: $ 35.6万
• 依托单位: Monash University
• 依托单位国家: 澳大利亚
• 项目类别: NHMRC Project Grants
• 财政年份: 2007
• 资助国家: 澳大利亚
• 起止时间: 2007-01-01 至 2009-12-31
• 项目状态: 已结题
• 来源: https://researchdata.edu.au/role-pipp-cell-polarization-proliferation/96735
• 关键词: role; PIPP; cell; polarization; proliferation.

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.

通常，仅当细胞收到刺激（例如激素或生长因子）时会分裂。刺激后，在细胞内产生了一系列信号，从而导致细胞分裂和发育。对生长因子刺激做出反应的信号通路之一是PI3-激酶途径。该途径与许多不同的人类癌症有关，当细胞无法控制并侵入周围的组织时，这种途径发生。遵循生长因子刺激，PI3-激酶产生一种称为PTDINS（3,4,5）P3的分子，该分子导致信号传导途径中许多蛋白质的激活。所有具有PI3-激酶的细胞也具有关闭PI3-激酶产生的信号的酶，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称为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的量并分析对细胞生长和发育的影响来研究PIPP的作用。我们还确定了许多与PIPP结合的蛋白质，我们将研究这些蛋白质在调节细胞信号传导中所起的作用。此外，我们计划通过产生缺乏PIPP（基因敲除小鼠）并评估对发育和癌症的影响的小鼠来表征PIPP在整个动物中的功能。