REGULATION OF ADP-RIBOSYLATION FACTOR

ADP-核糖基化因子的调节

• 批准号: 6435433
• 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/6435433
• 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 during cell movement and 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. The role of the Arf family of GTP-binding proteins has been our focus. We have found a family of GTPase-activating proteins (GAPs) for Arf, the ASAP/ACAP family, which contain PH, Arf GAP and ANK repeat domains. All tested members of the family function as GAPs in vitro. We have found that these proteins are specific for particular Arfs both in vitro and in vivo. In addition, the GAP activity of these proteins is dependent on two phospholipids, phosphatidic acid and a phosphoinositide. The different ASAP/ACAP family members also show specificity for the particular phospoinositide isomer, some being activated by phosphatatidylinositol 4,5 bisphosphate and others activated by phosphatidylinositol 3,4,5 trisphosphate. The PH domain regulates activity by a mechanism not previously described for this motif. Two members of the family have een found to bind Src and FAK family proteins, and one of these has been shown to regulate the cycle of events that result in cell migration. Current work is aimed at identifying the cellular functions of other members of the family, including a possible role of one member, which is found on a chromosomal locus linked to neuroblastoma, in malignant transformation. Z01 BC 07365-03 LBC to LCO

生物膜在细胞运动期间和在细胞器之间转移物质同时保持细胞器身份的过程中经历连续重塑，并影响通过有丝分裂进展所必需的细胞器的组装和重新组装。本实验室工作的主要目的是阐明调节膜重塑的机制。GTP结合蛋白Arf家族的作用一直是我们关注的焦点。 我们已经发现了一个ASAP/ACAP家族，该家族含有PH、Arf GAP和ANK重复结构域。所有测试的家族成员在体外都作为GAP起作用。 我们已经发现，这些蛋白质是特定的Arfs在体外和体内。 此外，这些蛋白质差距活性依赖于两种磷脂，磷脂酸和磷酸肌醇。不同的ASAP/ACAP家族成员还显示出对特定的肌醇磷脂异构体的特异性，一些被磷脂酰肌醇4，5二磷酸活化，而另一些被磷脂酰肌醇3，4，5三磷酸活化。 PH结构域通过先前未描述的机制调节活性。已经发现该家族的两个成员结合Src和FAK家族蛋白，并且其中一个已经显示出调节导致细胞迁移的事件的周期。目前的工作旨在确定该家族其他成员的细胞功能，包括在恶性转化中发现的与神经母细胞瘤相关的染色体位点上的一个成员的可能作用。 Z 01 BC 07365-03 LBC至LCO