SIGNALING MECHANISMS AND REGULATION OF THE PDGF ALPHA RECEPTOR

血小板衍生生长因子（PDGF）的三种亚型，两种PDGF 受体，并且PDGF系统调节的生化过程是 对我们理解生长控制和许多医学 问题 因为PDGF α受体最近才被描述， 关于PDGF的这一成分，克隆的信息较少 系统 这项研究的总体目标是阐明 α受体的功能。 我们的具体目标旨在 确定调节PDGF表达的细胞机制 α受体 我们将研究控制正常水平的 α受体和调节PDGF的合成控制类型 α-受体在被配体下调后立即表达 约束力 本申请旨在研究和比较alpha和beta PDGF受体在特定的细胞周期时间刺激过程。 我们将 确定α和β PDGF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 PDGF α受体对Ca++的依赖性有限， β受体对Ca++浓度的影响。 我们将确定机制 由此β-受体刺激的过程不同于 那些受α-受体刺激的细胞， Ca++。 我们的最后一个具体目标旨在确定增长的差异 通过PDGF-AA与PDGF-BB的刺激。 我们的初步数据清楚地表明 PDGF-BB刺激感受态形成， 电池只需要4小时。 然而，刺激细胞增殖， PDGF-AA需要PDGF-AA持续存在。 我们的理解 α和β PDGF受体的差异和相似之处是 这一点很重要，因为很明显，PDGF的同种型和受体 型在生长和发育过程中用作调节机制， 可能用于其它细胞类型。 有必要了解其功能 为了清楚地了解PDGF的功能， 控制生长。 完成这些具体目标的实验将 需要抗体的开发和分子生物学的使用， 生产特异性载体并克隆感受态所需的基因 PDGF-BB诱导的状态，而PDGF-AA不诱导。

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.