LIGAND DEPENDENT SIGNALING BY ERBB-4

HERG配体的三种不同的异构体 在细菌中表达和纯化的基因被克隆和分子 特征；它们是生物学研究的来源 在NIH/3T3和32D系统上进行。这些细胞已经被转基因 用erbB-2、erbB-3和erbB-4原癌基因阐明其在肿瘤转移中的作用 HRG配体可能具有结合、触发、生物和 这些酪氨酸激酶受体的生化激活。 克隆了ergB-4原癌基因，并对其进行了分子特征分析。和 嵌合受体表皮生长因子(EGF)/erbB-4与 表皮生长因子受体(EGFR)的胞外区和 ErbB-4酪氨酸激酶的胞内结构域是遗传的 为了进行生化级联途径的研究而设计的 在EGF触发下对猪的erbB-4的激活 3-激酶PLC-A。GTP酶激活蛋白(GAP)与Shc募集。 更重要的是。基于密切的结构相似和频繁 ErbB-2和erbB-3在正常细胞和人卵巢癌组织中的共表达 上皮起源，一项研究正在进行中，以指示可能的 这些受体在信号通路中的协同作用。

Three different isoforms of the heregulin ligands which have been expressed in bacteria and purified were cloned and molecularly characterized; they are the source for the biological studies that were conducted on NIH/3T3 and 32D systems. These cells have been transfected with erbB-2, erbB-3 and erbB-4 proto-oncogenes to elucidate the role that the HRG ligands may have on binding, triggering, biological and biochemical activation of those tyrosine kinase receptors. The ergB-4 proto-oncogene was cloned and molecularly characterized. and a chimeric receptor epidermal growth factor (EGF)/erbB-4 with the extracellular domain of the epidermal growth factor receptor (EGFR) and the intracellular domains of the erbB-4 tyrosine kinase was genetically engineered in order to perform studies on the biochemical cascade pathway of activation of erbB-4 upon EGF triggering with particular regard to PI 3-kinase PLC-A. GTPase activating protein (GAP) and Shc recruitment. Furthermore. based upon close structural similarity and frequent coexpression of erbB-2 and erbB-3 in normal cells and human tumors of epithelial origin, a study is in progress to denote the possible cooperative function of these receptors in signaling pathways.