A 1.8 kb alternative transcript from the human epidermal growth factor receptor gene encodes a truncated form of the receptor.
A 1.8 kb alternative transcript from the human epidermal growth factor receptor gene encodes a truncated form of the receptor.
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DOI：
10.1093/nar/24.20.4050
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发表时间：
1996-10
影响因子：
14.9
通讯作者：
Jill L. Reiter;Nita J. Maihle
中科院分区：
文献类型：
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作者：
Jill L. Reiter;Nita J. Maihle
表皮生长因子受体（EGFR）是由c-erbB 1原癌基因编码的，在控制细胞生长和分化中起重要作用。为了研究可溶性EGF受体的潜在生长调节作用，我们分离了编码截短的分泌型人EGFR的cDNA克隆。该cDNA的5'序列与编码全长受体的EGFR转录物的外显子10相同。独特的3'序列在遇到框内终止密码子之前编码两个额外的氨基酸残基，即poly（A）添加位点和poly（A）+尾。与基因组DNA序列的序列比较表明，这种替代性转录本是通过剪接供体位点的通读而产生的。因此，该转录本编码部分细胞外配体结合结构域，但缺乏EGFR中存在的跨膜结构域和细胞内酪氨酸激酶催化结构域。来自转染的成纤维细胞的条件培养基含有60 kDa的蛋白质，该蛋白质被EGFR单克隆抗体特异性免疫沉淀。这些发现表明，人EGFR转录物的替代加工产生仅由胞外配体结合结构域组成的分泌产物。
The epidermal growth factor receptor (EGFR) is encoded by the c-erbB1 proto-oncogene and plays an important role in the control of cell growth and differentiation. To study the potential growth regulatory role of soluble EGF receptors, we have isolated cDNA clones encoding a truncated, secreted form of the human EGFR. The 5' sequence of this cDNA is identical to the EGFR transcript encoding the full-length receptor through exon 10. The unique 3' sequence encodes two additional amino acid residues before encountering an in-frame stop codon, a poly(A) addition site and a poly(A)+ tail. Sequence comparison with genomic DNA sequences demonstrates that this alternative transcript arises by read-through of a splice donor site. As a result, this transcript encodes a portion of the extracellular ligand-binding domain, but lacks the transmembrane domain and the intracellular tyrosine kinase catalytic domain present in the EGFR. Conditioned medium from transfected fibroblast cells contains a 60 kDa protein that is specifically immunoprecipitated by an EGFR monoclonal antibody. These findings demonstrate that alternative processing of the human EGFR transcript produces a secreted product composed of only the extracellular ligand-binding domain.