METABOLISM OF THE EGF-RECEPTOR AND ERBB PROTEIN

表皮生长因子(EGF)受体及其受体代谢的研究 ErbB蛋白将继续存在。这些研究应该有助于 对细胞调控的一些机制的理解 高等生物体中的分部。表皮生长因子受体与血管生成的关系 ErbB蛋白介导的有丝分裂和蛋白的磷酸化 酪氨酸残留量将使用针对这些蛋白质的抗体进行检测。 和抗磷酸酪氨酸抗体。酪氨酸在体内的作用 表皮生长因子受体和erb B蛋白各自的磷酸化 活动将被确定。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和 禽红母细胞病病毒(AEV)转化细胞。这些蛋白质可能 在触发细胞分裂中发挥作用。我们会特别注意 对酪氨酸磷酸化的膜蛋白的鉴定和 与EFG的酪氨酸磷酸化形式相关的蛋白质 受体和erbB蛋白。肿瘤促进剂的作用机制 减弱EGF受体和erbB蛋白的有丝分裂信号将是 走近了。肿瘤促进剂对血管内皮细胞酪氨酸磷酸化的影响 蛋白质将被测定。细胞将被AEV转化为含有 ErbB蛋白在苏氨酸98位或其附近发生突变(苏氨酸在 对肿瘤促进剂治疗细胞的反应)。这些细胞将是 评估对肿瘤促进剂的改变反应。血小板的作用 衍生生长因子对EGF受体功能的影响也将被研究。 羧基末端截短的erbB蛋白与全长蛋白的代谢 将研究长度为羧基末端的erbB蛋白 生物合成、周转、细胞内定位、激酶活性和 致癌性。老年高血压患者EGF受体代谢异常的研究 人乳腺癌细胞系MDA-MB-231将继续重点 从这些细胞中鉴定含有内小体的EGF受体。 EGF受体的磷酸化也将被更彻底地检测。 在这些牢房里。沙门氏菌c-erbB蛋白的初步鉴定 果蝇将开始使用针对重组人制备的抗血清 蛋白。一个M=100,000果蝇生长因子结合蛋白的分析 会继续下去。V-erba和c-erba蛋白的结构比较 将再次使用针对重组体制备的抗血清进行 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.