ANALYSIS OF PDGF RECEPTOR ROLE IN NEOPLASTIC TRANSFORMATION

我们鉴定了一个基因组序列，并克隆了一个新的 血小板衍生生长因子受体的受体样基因 集落刺激因子-1受体亚家族。该基因被识别 一个6.4 kb的转录本，在正常人体组织中与 5.3kb的PDGF受体基因。其基因在COS-1细胞中的表达导致 三者竞争的125I-人PDGF的特异性结合 PDGF异构体。人血小板衍生生长因子受体基因在COS-1细胞中的表达 导致PDGF与同一PDGF结合具有不同的竞争模式 异构体。编码两种相互作用的PDGF受体的基因的存在 以一种不同的方式与三种不同的PDGF亚型可能授予 在对PDGF的功能反应中具有相当大的调节灵活性。 为了研究每个受体特有的功能反应， 我们致力于在正常情况下缺乏的细胞中表达它们的cDNA。 任何一个感受器。我们证明了这两种受体都可以在 并且每个细胞独立地调节已知的主要PDGF活动 包括有丝分裂信号转导、趋化和刺激 肌醇磷脂周转率。不同PDGF异构体与它们的结合 从功能上区分两种受体基因产物，并建立 新发现的α-PDGF受体是人PDGF的首选受体。

We identified a genomic sequence and cloned the cDNA of a novel receptor-like gene of the platelet-derived growth factor (PDGF) receptor colony-stimulating factor-1 (CSF-1) receptor subfamily. The gene recognized a 6.4-kb transcript that was coexpressed in normal human tissues with the 5.3-kb PDGF receptor mRNA. The expression of its cDNA in COS-1 cells led to the specific binding by 125 I-human PDGF which was competed by all three PDGF isoforms. Expression of the known PDGF receptor cDNA in COS-1 cells led to PDGF binding with a distinct pattern of competition by the same PDGF isoforms. The existence of genes encoding two PDGF receptors that interact in a distinct manner with three different PDGF isoforms likely confers considerable regulatory flexibility in the functional response to PDGF. In order to investigate the functional responses specific to each receptor, we undertook efforts to express their cDNAs in cells normally devoid of either receptor. We demonstrated both that receptors can function in such cells and that each independently mediates major known PDGF activities including mitogenic signal transduction, chemotaxis and stimulation of phosphoinositide turnover. Their binding by different PDGF isoforms distinguishes the two receptor gene products functionally and establishes the newly identified alpha PDGF receptor as the preferred for human PDGF.