Role of tyrosine kinase and membrane-spanning domains in signal transduction by the platelet-derived growth factor receptor.
Role of tyrosine kinase and membrane-spanning domains in signal transduction by the platelet-derived growth factor receptor.
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酪氨酸激酶和跨膜结构域在血小板衍生生长因子受体信号转导中的作用。
DOI：
10.1128/mcb.8.12.5126-5131.1988
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发表时间：
1988
影响因子：
5.3
通讯作者：
Williams,LT
中科院分区：
文献类型：
--
作者：
Escobedo,JA;Barr,PJ;Williams,LT
三种类型的突变被引入血小板衍生生长因子（PDGF）受体，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，和（iii）跨膜序列被其他受体的类似跨膜序列取代。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诱导的受体下调是正常的突变细胞。这些结果表明，跨膜序列具有特定的信号转导功能，而不仅仅是作为一个膜锚和受体激酶活性是必需的大多数响应PDGF，但不是必需的受体下调。
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.