Reiter J L, Maihle N J
Department of Biochemistry and Molecular Biology, Mayo Clinic, Rochester, Minnesota 55905, USA.
Nucleic Acids Res. 1996 Oct 15;24(20):4050-6. doi: 10.1093/nar/24.20.4050.
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.
表皮生长因子受体（EGFR）由c-erbB1原癌基因编码，在细胞生长和分化的调控中发挥重要作用。为研究可溶性EGF受体的潜在生长调节作用，我们分离了编码人EGFR截短型分泌形式的cDNA克隆。该cDNA的5'序列与编码全长受体直至外显子10的EGFR转录本相同。独特的3'序列在遇到框内终止密码子之前编码另外两个氨基酸残基、一个聚腺苷酸添加位点和一个聚腺苷酸尾。与基因组DNA序列的比对表明，这种可变转录本是由剪接供体位点的通读产生的。因此，该转录本编码细胞外配体结合域的一部分，但缺乏EGFR中存在的跨膜域和细胞内酪氨酸激酶催化域。转染的成纤维细胞条件培养基中含有一种60 kDa的蛋白，该蛋白可被EGFR单克隆抗体特异性免疫沉淀。这些发现表明，人EGFR转录本的可变加工产生了一种仅由细胞外配体结合域组成的分泌产物。
