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

使用v-erbB作为探针，在杂交严格性降低的情况下，我们已经 鉴定出最接近同源性的一个新的erb相关基因的三个外显子 和67%到酪氨酸激酶结构域的邻接区 分别为血小板衍生生长因子受体(PDGFR)。Cdna 克隆揭示了一个预测的148 kodalton跨膜多肽 鉴定其为erbB/表皮的第三个成员的结构特征 生长因子受体(EGFR)家族，促使我们将该基因指定为 ErbB-3。它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，一个跨膜，以及它的 胞质酪氨酸激酶结构域不间断，分别为81%和83% 与EGFR和erbB-2产品的总体相似性显著高于 任何其他酪氨酸酶。用原位杂交技术定位人erbB-3基因 与染色体12ql3杂交，并显示表达为 6.2kb转录本在多种正常组织中的表达 神经外胚层起源。显著升高的erbB-3mRNA水平 在某些乳腺肿瘤细胞系中显示出升高的 ErbB-3的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.