Characterization of the phosphoinositide 5-phosphatase SKIP.

磷酸肌醇 5-磷酸酶 SKIP 的表征。

• 批准号: nhmrc : 384137
• 负责人: Prof Christina Mitchell
• 金额: $ 33.71万
• 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: 2006
• 资助国家: 澳大利亚
• 起止时间: 2006-01-01 至 2008-12-31
• 项目状态: 已结题
• 来源: https://researchdata.edu.au/characterization-phosphoinositide-5-phosphatase-skip/76230
• 关键词: Characterization; phosphoinositide; phosphatase; SKIP.

Growth factors and insulin stimulate a complex array of signals inside the cell, which are important for both cell survival and metabolism. A central intracellular signaling enzyme that initiates lipid messages that promote glucose uptake into the cell and promote cell survival is that generated by the PI3-kinase. This enzyme has increased activity in many cancers, and is also important in diabetes when the enzyme may be suppressed. Our grant proposes to investigate the function of another enzyme called SKIP which acts within the cell to oppose the functions of the PI3-kinase. Several lines of evidence indicate SKIP may be important in both development and cancer. SKIP has been identified as a putative candidate gene for a developmental disorder known as Miller Dieker syndrome. This disease is associated with facial and significant brain abnormalities. In addition the SKIP gene is located on a chromosome that is frequently deleted in breast and colon cancer. SKIP is an enzyme that functions to remove phosphate molecules from PI3-kinase signaling molecules. SKIP has been shown to prevent glucose uptake into the cell by breaking down PI3-kinase signals. We have recently demonstrated SKIP phosphatase activity can be inhibited by binding to another protein called suppressor of death domains (SODD). We plan to investigate the effects this complex has on SKIP enzyme activity, and how this complex plays a role in regulating PI3-kinase signals that promote glucose uptake. Secondly, we plan to investigate the function of SKIP in an intact animal by making mice which lack SKIP(knock out mice). Given SKIP is implicated in a developmental syndrome and insulin signaling, we can delineate the functional significance of SKIP and the molecular pathways regulated by this enzyme.

生长因子和胰岛素刺激细胞内一系列复杂的信号，这对于细胞的生存和新陈代谢都很重要。 PI3 激酶产生一种核心细胞内信号酶，它启动脂质信息，促进细胞摄取葡萄糖并促进细胞存活。这种酶在许多癌症中的活性增加，并且在糖尿病中也很重要，因为该酶可能受到抑制。我们的资助计划研究另一种称为 SKIP 的酶的功能，该酶在细胞内发挥作用，对抗 PI3 激酶的功能。多项证据表明 SKIP 在发育和癌症中可能都很重要。 SKIP 已被确定为一种称为米勒迪克综合征的发育障碍的假定候选基因。这种疾病与面部和明显的大脑异常有关。此外，SKIP 基因位于乳腺癌和结肠癌中经常被删除的染色体上。 SKIP 是一种酶，其功能是从 PI3 激酶信号分子中去除磷酸分子。 SKIP 已被证明可以通过破坏 PI3 激酶信号来阻止细胞摄取葡萄糖。我们最近证明 SKIP 磷酸酶活性可以通过与另一种称为死亡抑制域 (SODD) 的蛋白质结合来抑制。我们计划研究该复合物对 SKIP 酶活性的影响，以及该复合物如何在调节促进葡萄糖摄取的 PI3 激酶信号中发挥作用。其次，我们计划通过制作缺乏SKIP的小鼠（敲除小鼠）来研究SKIP在完整动物中的功能。鉴于 SKIP 与发育综合征和胰岛素信号传导有关，我们可以描述 SKIP 的功能意义以及该酶调节的分子途径。