Wells A, Welsh J B, Lazar C S, Wiley H S, Gill G N, Rosenfeld M G
Department of Pathology, University of California-San Diego, La Jolla 92093.
Science. 1990 Feb 23;247(4945):962-4. doi: 10.1126/science.2305263.
Identification of a mutant epidermal growth factor (EGF) receptor that does not undergo downregulation has provided a genetic probe to investigate the role of internalization in ligand-induced mitogenesis. Contact-inhibited cells expressing this internalization-defective receptor exhibited a normal mitogenic response at significantly lower ligand concentrations than did cells expressing wild-type receptors. A transformed phenotype and anchorage-independent growth were observed at ligand concentrations that failed to elicit these responses in cells expressing wild-type receptors. These findings imply that activation of the protein tyrosine kinase activity at the cell membrane is sufficient for the growth-enhancing effects of EGF. Thus, downregulation can serve as an attenuation mechanism, without which transformation ensues.
一种不会发生下调的突变型表皮生长因子（EGF）受体的鉴定，为研究内化作用在配体诱导的有丝分裂中的作用提供了一种遗传探针。与表达野生型受体的细胞相比，表达这种内化缺陷型受体的接触抑制细胞在显著更低的配体浓度下表现出正常的有丝分裂反应。在表达野生型受体的细胞中未能引发这些反应的配体浓度下，观察到了转化表型和不依赖贴壁的生长。这些发现表明，细胞膜上蛋白酪氨酸激酶活性的激活足以产生EGF的生长促进作用。因此，下调可以作为一种衰减机制，没有这种机制就会发生转化。
