METABOLISM OF THE EGF-RECEPTOR

表皮生长因子（EGF）受体介导的有丝分裂的调控 将在正常和转化细胞中进行检查，并表征 将启动血小板衍生生长因子（PDGF）受体。 的 EGF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， 可能与受体肌醇磷脂激酶活性有关。 述受体是 已知与酪氨酸特异性蛋白激酶活性相关， 也可能具有肌醇磷脂激酶活性， 劳斯肉瘤病毒和UR2肉瘤病毒的src和ros基因产物， 分别 EGF受体制剂将在体外进行测定 肌醇磷脂激酶活性以及EGF和TPA对 将在体内测定肌醇磷脂代谢。 的 表皮生长因子受体的磷酸化参与运输过程中的G1 细胞周期的阶段将在研究的影响， PDGF对EGF受体磷酸化的影响 在无血清培养基中生长的成纤维细胞。 肌醇磷脂的作用 代谢和蛋白激酶C活性的协调过程， 还将研究PDGF和EGF系统。 EGF受体代谢 转化细胞中，异常形式的表皮生长因子受体发挥直接作用， 在转化依赖性生长控制丧失中的作用（禽 成红细胞增多症病毒转化的细胞和B104成神经细胞瘤细胞）或 其中EGF受体代谢改变的功能尚不清楚， 建立的（劳斯肉瘤病毒转化细胞）将在以下方面进行研究 通过受体磷酸化调节激酶活性，肌醇 磷脂代谢和受体的生物合成和降解。 将使用抗PDGF受体的单克隆和多克隆抗体。 为了启动有关PDGF的许多方面的工作， 受体在正常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)