Escobedo J A, Barr P J, Williams L T
Howard Hughes Medical Institute, University of California, San Francisco 94143-0724.
Mol Cell Biol. 1988 Dec;8(12):5126-31. doi: 10.1128/mcb.8.12.5126-5131.1988.
Three types of mutations were introduced into the platelet-derived growth factor (PDGF) receptor to cause a loss of PDGF-stimulated tyrosine kinase activity: (i) a point mutation of the ATP-binding site, (ii) a deletion of the carboxyl-terminal region, and (iii) replacement of the membrane-spanning sequences by analogous transmembrane sequences of other receptors. Transfectants expressing mutated receptors bind, 125I-labeled PDGF with a high affinity but had no PDGF-sensitive tyrosine kinase activity, phosphatidylinositol turnover, increase in the intracellular calcium concentration, change in cellular pH, or stimulation of DNA synthesis. However, PDGF-induced receptor down regulation was normal in the mutant cells. These results indicate that the transmembrane sequence has a specific signal-transducing function other than merely serving as a membrane anchor and that the receptor kinase activity is necessary for most responses to PDGF but is not required for receptor down regulation.
三种类型的突变被引入血小板衍生生长因子（PDGF）受体，以导致PDGF刺激的酪氨酸激酶活性丧失：（i）ATP结合位点的点突变，（ii）羧基末端区域的缺失，以及（iii）用其他受体的类似跨膜序列替换跨膜序列。表达突变受体的转染子以高亲和力结合125I标记的PDGF，但没有PDGF敏感的酪氨酸激酶活性、磷脂酰肌醇周转、细胞内钙浓度增加、细胞pH变化或DNA合成刺激。然而，PDGF诱导的受体下调在突变细胞中是正常的。这些结果表明，跨膜序列具有特定的信号转导功能，而不仅仅是作为膜锚，并且受体激酶活性对于大多数对PDGF的反应是必需的，但对于受体下调不是必需的。
