REGULATION OF PDGF RECEPTORS

血小板衍生生长因子(PDGF)是一种多肽生长因子， 最初是从血小板中分离出来的。有人提议释放PDGF 在伤口愈合中扮演有益的角色，在创伤中扮演有害的角色 动脉粥样硬化的病因学。现在已知PDGF由许多人分泌 不同细胞类型，并成为两种哺乳动物的原癌基因 逆转录病毒。这些观察结果激发了许多电流 对PDGF可能存在的可能性的调查和推测 参与正常组织发育的其他过程 重塑，以及致癌转化。大多数假设都是关于 PDGF的功能将PDGF受体视为其表达 统一不变，PDGF功能确定 完全通过调节PDGF的生产或释放。我们建议 检验假设：(1)PDGF受体表达受调控 在发育期间和急性组织对刺激的反应期间。(2)这个 血小板衍生生长因子受体的表达调控在血管紧张素转换酶中起重要作用 测定PDGF的生物学功能。 为了验证这些假设，我们将首先确定哪些细胞表达PDGF 正常成人组织中的受体，这种模式是如何在 胚胎发生，以及它如何对刺激做出反应。的表达 两个受体亚基都将被确定，因为我们的初步证据 提示这两个亚基是独立调节的，并可能起作用 在体内的功能略有不同。过程的细胞培养模型 受体表达的显示调控将进一步发展到 允许研究受体通过的分子机制 表达是受调控的。最后，我们将尝试确认假设 从实验操作看PDGF的生物学功能 受体在培养和体内的表达。

Platelet-derived growth factor (PDGF) is a polypeptide growth factor which was originally isolated from blood platelets. Release of PDGF was proposed to play a beneficial role in wound healing and a pernicious role in the etiology of atherogenesis. PDGF is now known to be secreted by many different cell types and to be the proto-oncogene of two mammalian retroviruses. These observations have stimulated much current investigation and speculation on the possibility that PDGF might be involved in additional processes of normal tissue development and remodeling, as well as in oncogenic transformation. Most hypotheses about the functions of PDGF treat the PDGF receptor as though its expression were uniform and unchanging, with the functions of PDGF being determined entirely through regulation of production or release of PDGF. We propose to test the hypotheses that: (1) PDGF receptor expression is regulated during development and during acute tissue responses to stimuli. (2) This regulation of PDGF receptor expression plays an important role in determining the biological functions of PDGF. To test these hypotheses we will first determine which cells express PDGF receptors in normal adult tissues, how this pattern is established during embryogenesis, and how it is altered in response to stimuli. Expression of both receptor subunits will be determined since our initial evidence suggests that the two subunits are independently regulated and may serve somewhat different functions in vivo. Cell culture models of precesses displaying regulation of receptor expression will be further developed to permit investigation into the molecular mechanisms through which receptor expression is regulated. Finally, we will attempt to confirm hypotheses about the biological functions of PDGF by experimentally manipulating receptor expression in culture and in vivo.