REGULATION OF ADP RIBOSYLATION FACTOR

ADP 核糖基化因子的调节

• 批准号: 6100902
• 负责人: P RANDAZZO
• 金额: --
• 依托单位: DIVISION OF BASIC SCIENCES - NCI
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/6100902
• 关键词: ADP ribosylation; binding proteins; cofactor; guanine nucleotide binding protein; guanosinetriphosphatase activating protein; hydrolysis; membrane biogenesis; phosphorylation; protein purification; protein structure function; protein transport

Biological membranes undergo continuous remodeling in processes that transfer material between organelles while maintaining organellar identity and affect the assembly and reassembly of organelles necessary for progression through mitosis. The main objective of the work in this laboratory is to elucidate the mechanisms that regulate the membrane remodeling involved in these processes. The role of the Arf family of GTP-binding proteins has been our focus. The hypothesis being tested is that regulating hydrolysis of GTP on Arf in turn regulates the consumption of protein coated vesicles that mediate membrane remodeling. Consistent with this model, a GTPase- activating protein (GAP) for Arf has been found to be specifically dependent on two phospholipids, phosphatidic acid and phosphatidylinositol 4,5-bisphosphate. The GAP has been purified and cloned. The sequence has revealed a number of domains that are likely relevant to function and regulation, including a 350 a.a. overlap with the general vesicular transport factor p115, a PH domain, a Zn finger domain, ankyrin repeats, a proline rich region including type 1 and type 2 ligands for SH3 domain binding, an SH3 domain, a potential cell cycle dependent kinase phosphorylation site and several potential MAP kinase phosphorylation sites. To test our hypothesis that modulation of Arf GAP regulates membrane remodeling, we will begin by focusing on the PH domain and potential phosphorylation sites.

生物膜经历持续的重塑过程， 在细胞器之间转移物质，同时保持细胞器 识别和影响必要的细胞器的组装和重组 通过有丝分裂的进展。这项工作的主要目标是 实验室的目的是阐明调节膜的机制， 重塑参与了这些过程。Arf家族的作用 GTP结合蛋白一直是我们研究的重点。 正在测试的假设是，调节Arf上GTP的水解， 进而调节蛋白质包被的囊泡的消耗， 介导膜重塑。与这个模型一致，一个GTTT- 已发现Arf的活化蛋白（GAP）特异性地 依赖于两种磷脂，磷脂酸和 磷脂酰肌醇4，5-二磷酸。差距已被纯化， 克隆的这个序列揭示了一些区域 与职能和管理有关的，包括350 a.a.重叠 一般囊泡转运因子p115，PH结构域，锌指 结构域，锚蛋白重复序列，富含脯氨酸的区域，包括1型和2型 2个SH 3结构域结合配体，一个SH 3结构域，一个潜在的细胞周期 依赖性激酶磷酸化位点和几种潜在的MAP激酶 磷酸化位点。为了验证我们的假设， 调节膜重塑，我们将开始重点关注PH值 结构域和潜在的磷酸化位点。