METABOLISM OF THE EGP-RECEPTOR AND ERB B PROTEIN

表皮生长因子（EGF）受体代谢的研究 erbB蛋白会继续存在 这些研究应有助于 了解一些参与细胞调节的机制， 高等生物的分裂。 EGF受体与 erbB蛋白介导的有丝分裂和蛋白质磷酸化 酪氨酸残基将使用针对这些蛋白质的抗体进行检查 和抗磷酸酪氨酸抗体。 体内酪氨酸的作用 EGF受体和erbB蛋白在其各自的 活动将确定。 抗磷酸酪氨酸抗体将是 用于从EGF处理的细胞中分离酪氨酸磷酸化蛋白， 禽成红细胞增多症病毒（AEV）转化的细胞。 这些蛋白质可能 在触发细胞分裂中发挥作用。 将特别注意 涉及酪氨酸磷酸化膜蛋白的鉴定， 与EFG的酪氨酸磷酸化形式相关的蛋白质 受体和erbB蛋白。 肿瘤促进剂 减弱EGF受体和erbB蛋白的促有丝分裂信号传导， 走近。 肿瘤促进剂对酪氨酸磷酸化的影响 蛋白质将被确定。 细胞将被含有以下物质的AEV转化： erbB蛋白在苏氨酸98处或附近突变（其在细胞中被磷酸化）。 细胞对肿瘤促进剂处理的反应）。 这些细胞将 评估对肿瘤促进剂的反应改变。 血小板的作用 还将研究衍生生长因子对EGF受体功能的影响。 羧基端截短erbB蛋白与完全erbB蛋白的代谢 长度羧基末端erbB蛋白将被研究， 生物合成，周转，细胞内定位，激酶活性和 致瘤性 表皮生长因子受体异常代谢的研究 MDA-MB-231人乳腺癌细胞系将继续重点关注 表皮生长因子（EGF）受体在这些细胞中的表达。 EGF受体的磷酸化也将得到更彻底的检查 在这些细胞中。 C-erbB蛋白的初步鉴定 果蝇将开始使用抗重组 蛋白 M= 100，000果蝇生长因子结合蛋白的分析 将继续 v-erbA和c-erbA蛋白的结构比较 将再次使用针对重组的 蛋白

Studies of the metabolism of the epidermal growth factor (EGF) receptor and the erbB protein will continue. These studies should contribute to the understanding of some of the mechanisms involved in regulation of cell division in higher organisms. The relationship between EGF receptor and erbB protein mediated mitogenesis and phosphorylation of proteins on tyrosine residues will be examined using antibodies against these proteins and anti-phosphotyrosine antibodies. The effects of in vivo tyrosine phosphorylation of the EGF receptor and erbB protein on their respective activities will be determined. Anti-phosphotyrosine antibodies will be used to isolate tyrosine phosphorylated proteins from EGF treated cells and avian erythroblastosis virus (AEV) transformed cells. These proteins may play a role in triggering cell division. Particular attention will be paid to the identification of tyrosine phosphorylated membrane proteins and proteins which associate with the tyrosine phosphorylated forms of the EFG receptor and erbB proteins. The mechanism through which tumor promoters attenuate mitogenic signalling of the EGF receptor and erbB protein will be approached. The effects of tumor promoters on tyrosine phosphorylation of proteins will be determined. Cells will be transformed by AEV containing erbB protein mutated at or near threonine 98 (which is phosphorylated in response to tumor promoter treatment of cells). These cells will be assessed for altered responses to tumor promoters. The effects of platelet derived growth factor on EGF receptor function will also be investigated. The metabolism of carboxy terminus truncated erbB protein versus full length carboxy terminus erbB protein will be studied with respect to biosynthesis, turnover, intracellular localization, kinase activity and oncogenicity. Study of the unusual metabolism of the EGF receptor in the MDA-MB-231 human breast cancer cell line will continue with emphasis on characterization EGF receptor containing endosomes from these cells. Phosphorylation of the EGF receptor will also be more thoroughly examined in these cells. Initial characterization of the c-erbB protein from Drosophila will be begun using antisera prepared against recombinant protein. Analysis of a M=100,000 Drosophila growth factor binding protein will continue. Structural comparison of the v-erbA and c-erbA proteins will be performed, again, using antiserum prepared against recombinant protein.