LIGAND-INDUCED TRANSFORMATION BY A NONINTERNALIZING EPIDERMAL GROWTH-FACTOR RECEPTOR
LIGAND-INDUCED TRANSFORMATION BY A NONINTERNALIZING EPIDERMAL GROWTH-FACTOR RECEPTOR
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DOI：
10.1126/science.2305263
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发表时间：
1990-02-23
期刊：
影响因子：
56.9
通讯作者：
ROSENFELD, MG
中科院分区：
文献类型：
--
作者：
WELLS, A;WELSH, JB;ROSENFELD, MG
突变的表皮生长因子(EGF)受体的鉴定为研究内化在配体诱导的有丝分裂中的作用提供了一个遗传探针。与表达野生型受体的细胞相比，表达这种内化缺陷受体的接触抑制细胞在显著较低的配体浓度下表现出正常的有丝分裂反应。当配体浓度不能在表达野生型受体的细胞中引起这些反应时，观察到转化的表型和锚定无关的生长。这些发现表明，激活细胞膜上的蛋白酪氨酸激酶活性足以发挥EGF的生长促进作用。因此，下调监管可以作为一种衰减机制，如果没有这种机制，就会发生变化。
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.