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部的一系列信号阵列，这对于细胞存活和代谢都很重要。一种启动脂质消息的中央细胞内信号传导酶，可促进葡萄糖吸收到细胞中并促进细胞存活。这种酶在许多癌症中的活性增加，并且在抑制酶时在糖尿病中也很重要。我们的赠款建议研究另一种称为Skip的酶的功能，该酶在细胞内作用以反对PI3-激酶的功能。几条证据表明，跳过在发育和癌症中都可能很重要。 Skip已被确定为被称为Miller Dieker综合征的发育障碍的假定候选基因。该疾病与面部和明显的大脑异常有关。此外，跳过基因位于经常在乳腺癌和结肠癌中删除的染色体。跳过是一种从PI3-激酶信号分子中去除磷酸分子的酶。已经证明跳过可以通过分解PI3-激酶信号来防止葡萄糖吸收进入细胞。我们最近证明，通过与另一种称为死亡结构域抑制因子（SODD）的蛋白质结合来抑制跳过磷酸酶活性。我们计划研究该复合物对跳过酶活性的影响，以及该复合物如何在调节促进葡萄糖摄取的PI3-激酶信号中起作用。其次，我们计划通过使缺乏跳过的小鼠（敲出小鼠）来研究Intact Animal中跳过的功能。给定跳过的发育综合征和胰岛素信号传导涉及，我们可以描述跳过的功能意义以及该酶调节的分子途径。