SIGNALING MECHANISMS AND REGULATION OF THE PDGF ALPHA RECEPTOR

血小板衍生生长因子(PDGF)的三种异构体、两种PDGF 受体，以及PDGF系统调节的生化过程是 对我们理解生长控制和众多医学知识很重要 有问题。因为PDGFα受体是最近才被描述的 关于PDGF的这一组成部分，克隆的信息较少 系统。这项拟议研究的总体目标是阐明 阿尔法受体的功能。我们的具体目标是 确定调控PDGF表达的细胞机制 阿尔法受体。我们将调查对正常水平的控制 α-受体与调节PDGF的合成控制类型 α-受体被配体下调后立即出现 有约束力的。这个应用程序试图研究和比较阿尔法和贝塔 PDGF受体在特定的细胞周期时间刺激细胞进程。我们会 确定α和βPDGF受体控制的细胞过程 在特定的细胞周期时间。此外，我们还将确定依赖关系 与PDGFα受体对钙离子的有限依赖性相比 β受体对钙离子浓度的影响。我们将确定其机制 因此，由β受体刺激的过程不同于 受α受体刺激的细胞对外部刺激的需求 CA++。我们的最后一个具体目标是确定增长的差异 PDGF-AA刺激与PDGF-BB刺激的比较。我们的初步数据清楚地表明 PDGF-BB刺激能力形成和PDGF-BB暴露于 电池只需要4小时。然而，通过刺激细胞增殖， PDGF-AA要求PDGF-AA持续存在。我们的理解 α和βPDGF受体的不同和相似之处在于 这一点很重要，因为很明显，PDGF的异构体和受体 类型在生长和发育过程中被用作一种调节机制 可能是针对其他类型的细胞。有必要了解它的功能 为了更清楚地了解PDGF的功能 在增长控制方面。完成这些特定目标的实验将 要求抗体的发展和分子生物学的使用 生产特定的载体并克隆能力所需的基因 PDGF-BB诱导的状态，PDGF-AA不诱导的状态。

The three isoforms of platelet-derived growth factor (PDGF), the two PDGF receptors, and the biochemical processes that the PDGF system regulate is important to our understanding of growth control and numerous medical problems. Because the PDGF alpha-receptor was only recently described and cloned less information is available concerning this component of the PDGF system. The overall goal of this proposed research is to elucidate the function of the alpha-receptor. Our Specific Aims are designed to determine the cellular mechanisms regulating the expression of the PDGF alpha-receptor. We will investigate the control of the normal level of alpha-receptors and the type of synthesis control that regulates the PDGF alpha-receptor immediately after it has been down-regulated by ligand binding. This application seeks to study and compare the alpha and beta PDGF receptor stimulated processes at specific cell cycle times. We will determine the cell processes that the alpha and beta PDGF receptor controls at specific cell cycle times. In addition we will determine the dependency of the PDGF alpha-receptor on Ca++ as compared to the limited dependency of the beta-receptor on Ca++ concentrations. We will determine the mechanism whereby the process stimulated by the beta-receptor are different from those stimulated by the alpha-receptor in their requirement for external Ca++. Our last Specific Aim seeks to determine the difference in growth stimulation by PDGF-AA versus PDGF-BB. Our preliminary data clearly shows that PDGF-BB stimulates competence formation and the PDGF-BB exposure to cells only requires 4 hrs. However, stimulation of cell proliferation by PDGF-AA requires the PDGF-AA to be present continuously. Our understanding of the differences and similarities of the alpha and beta PDGF receptor are important because it is apparent that the isoform of PDGF and the receptor type is used as a regulatory mechanism during growth and development and possibly for other cell types. It is necessary to understand the function of the alpha-receptor in order to clearly understand the function of PDGF in growth control. Experiments to complete these Specific Aims will require the development of antibody and the use of molecular biology to produce specific vectors and to clone the genes required for the competence state induced by PDGF-BB but not induced by PDGF-AA.