METABOLISM OF THE EGF-RECEPTOR

表皮生长因子受体介导的有丝分裂调控 将在正常和转化的细胞中进行检测，并表征 血小板衍生生长因子(PDGF)受体将启动。这个 促肾上腺皮质激素释放激素受体磷酸化的功能意义 EGF或肿瘤促进剂将在体内和体外进行研究 磷酸化对受体蛋白激酶活性的影响 可能是对受体肌醇磷脂蛋白激酶活性的影响。受体是 已知与酪氨酸特异性蛋白激酶活性有关，并 也可能具有最近发现的肌醇磷脂激酶活性 Rous肉瘤病毒和UR2肉瘤病毒的src和ros基因产物， 分别进行了分析。EGF受体制剂将在体外进行检测 肌醇磷脂蛋白激酶活性及EGF和TPA对其影响 肌醇磷脂代谢将在体内进行测定。这个 G1期转运过程中EGF受体磷酸化的参与 细胞周期的时相将在研究中确定 PDGF对人同步培养的EGF受体磷酸化的影响 成纤维细胞在无血清培养液中生长。肌醇磷脂的作用 协调过程中的代谢和蛋白激酶C活性 还将对PDGF和EGF系统进行研究。血管内皮细胞生长因子受体代谢 转化的细胞中EGF受体的异常形式直接起到了 在依赖转化的生长控制丧失中的作用(AVEN 红母细胞病病毒转化细胞和B104神经母细胞瘤细胞)或 其中改变的EGF受体代谢的功能尚不清楚 已建立的(劳斯肉瘤病毒转化细胞)将在 通过受体磷酸化，肌醇来调节激酶活性 磷脂代谢，以及受体的生物合成和降解。 抗PDGF受体的单抗和多克隆抗体将 为启动关于PDGF许多方面的工作而进行的准备 受体在正常细胞和转化细胞中的功能。(J)

Regulation of epidermal growth factor (EGF) receptor-mediated mitogenesis will be examined in normal and transformed cells and characterization of the platelet-derived growth factor (PDGF) receptor will be initiated. The functional significance of phosphorylation of the EGF receptor induced by EGF or tumor promoters will be investigated in vivo and in vitro in regard to the effects of phosphorylation on receptor protein kinase activity and perhaps on receptor inositol phosphatide kinase activity. The receptor is known to be associated with tyrosine-specific protein kinase activity and may also possess inositol phosphatide kinase activity as recently found for the src and ros gene products of Rous sarcoma virus and UR2 sarcoma virus, respectively. EGF receptor preparations will be assayed for in vitro inositol phosphatide kinase activity and the effects of EGF and TPA on inositol phosphatide metabolism will be determined in vivo. The involvement of EGF receptor phosphorylation during transit of the G1 phase of the cell cycle will be established in studies of the effects of PDGF on EGF receptor phosphorylation using synchronous cultures of human fibroblasts grown in serum-free medium. The roles of inositol phosphatide metabolism and protein kinase C activity in coordinate processes involving the PDGF and EGF systems will also be studied. EGF receptor metabolism in transformed cells in which abnormal forms of the EGF receptor play a direct role in transformation-dependent loss of growth control (avian erythroblastosis virus-transformed cells and B104 neuroblastoma cells) or in which the function of altered EGF receptor metabolism is not clearly established (Rous sarcoma virus transformed cells) will be studied in terms of regulation of kinase activity through receptor phosphorylation, inositol phosphatide metabolism, and receptor biosynthesis and degradation. Monoclonal and polyclonal antibodies against the PDGF receptor will be prepared in order to initiate work concerning the numerous aspects of PDGF receptor function in normal and transformed cells. (J)