REGULATION OF ADP RIBOSYLATION FACTOR

生物膜经历了持续的重塑过程， 在保持细胞器的同时在细胞器之间转移物质 确定并影响必要的细胞器的组装和重新组装 以促进有丝分裂的进展。这项工作的主要目标是 实验室的任务是阐明膜的调节机制 参与这些过程的重塑。阿尔夫家族的作用 GTP结合蛋白一直是我们关注的焦点。 正在测试的假设是调节Arf上GTP的水解度 进而调节蛋白质包被囊泡的消耗， 介导膜重塑。与这个模型一致的是，一种GTP酶- 已发现Arf的激活蛋白(GAP)是特异的 依赖于两种磷脂，磷脂酸和 磷脂酰肌醇4，5-二磷酸。GAP已经被净化，并且 克隆的。该序列揭示了一些结构域，很可能是 与职能和法规相关，包括350 A.A.与以下内容重叠 一般囊泡转运因子p115、一个PH结构域、一个锌指 结构域，Ankyrin重复，一个富含Pro的区域，包括类型1和类型 2个SH3结构域结合的配体，一个SH3结构域，一个潜在的细胞周期 依赖蛋白激酶磷酸化位点与几种潜在的MAP蛋白激酶 磷酸化位点。为了验证我们的假设，Arf间隙的调制 调节膜重塑，我们将从关注PH开始 结构域和潜在的磷酸化位点。

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.