AN EXPANDING FAMILY OF ERBB/EGF RECEPTOR-LIKE TYROSINE KINASES

在降低的杂交严格性下使用v-erbB作为探针，我们得到 确定了一个新的erbB相关基因的三个外显子， 64%和67%的酪氨酸激酶结构域内的连续区域， 血小板衍生生长因子受体（PDGFR）。cDNA 克隆揭示了预测的148千道尔顿跨膜多肽， 结构特征将其确定为erbB/表皮的第三个成员 生长因子受体（EGFR）家族，促使我们将该基因命名为 erbB-3。其预测的蛋白质结构包括一个胞外结构域 有两个标志性的半胱氨酸簇，一个单一的跨膜， 不间断的胞质酪氨酸激酶结构域分别显示81%和83%的 EGFR和erbB-2产品的总体相似性显著高于 任何其他酪氨酸激酶。人erbB-3基因的原位定位 与染色体12 q13杂交，并显示表达为 6.2-在多种正常的上皮组织中， 神经外胚层起源erbB-3 mRNA水平显著升高， 在某些乳腺肿瘤细胞系中证实， erbB-3表达可能在某些人类恶性肿瘤中起作用。

Using v-erbB as a probe under reduced hybridization stringency, we have identified three exons of a novel erbB-related gene with closest identity of 64% and 67% to a contiguous region within the tyrosine kinase domains of the platelet-derived growth factor receptor (PDGFR), respectively. cDNA cloning revealed a predicted 148-kilodalton transmembrane polypeptide with structural features identifying it as a third member of the erbB/epidermal growth factor receptor (EGFR) family, prompting us to designate the gene as erbB-3. Its predicted protein structure includes an extracellular domain with two signature cysteine clusters, a single transmembrane, and its uninterrupted cytoplasmic tyrosine kinase domain exhibiting 81% and 83% significantly greater overall similarities to EGFR and erbB-2 products than to any other tyrosine kinase. The human erbB-3 gene was mapped by in situ hybridization to chromosome 12ql3 and shown to be expressed as a 6.2-kilobase transcript in a variety of normal tissues of epithelial and neuroectodermal origin. Markedly elevated erbB-3 mRNA levels were demonstrated in certain mammary tumor cell lines suggesting that elevated erbB-3 expression may play a role in some human malignancies.