LIGAND DEPENDENT SIGNALING BY ERBB-4

已被证实的调蛋白配体的三种不同亚型 在细菌中表达并纯化， 它们是生物学研究的来源， 在NIH/3 T3和32 D系统上进行。这些细胞已经被转染 与erbB-2、erbB-3和erbB-4原癌基因一起，以阐明 HRG配体可以具有结合、触发、生物和 这些酪氨酸激酶受体的生化激活。 克隆了ergB-4原癌基因并进行了分子鉴定。和 嵌合受体表皮生长因子（EGF）/erbB-4， 表皮生长因子受体（EGFR）的细胞外结构域， erbB-4酪氨酸激酶的细胞内结构域在遗传上是 为了进行生化级联途径的研究， EGF触发时erbB-4的激活，特别是PI 3-激酶PLC-A。GTP酶激活蛋白（GAP）和Shc募集。 此外。基于紧密的结构相似性和频繁 erbB-2和erbB-3在正常细胞和人类肿瘤中的共表达 上皮起源，一项研究正在进行中，以表明可能的 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.