PDGF alpha‐ and beta‐receptors activate unique and common signal transduction pathways.
PDGF alpha‐ and beta‐receptors activate unique and common signal transduction pathways.
复制标题
PDGF α 和 β 受体激活独特且常见的信号转导途径。
作者：
A. Eriksson;A. Siegbahn;Bengt Westermark;C. Heldin;Lena Claesson
我们已经检查了PDGF α和β受体的信号转导途径，以表征信号传导中每种受体类型的特异性。建立了表达相同水平PDGF α或β受体的猪主动脉内皮细胞系。α和β受体细胞对适当的PDGF同种型刺激有促有丝分裂反应。肌动蛋白重组的三个方面进行了研究后，配体刺激：应力纤维的损失，边缘皱褶的外观和环形膜皱褶的形成。β受体细胞显示出对配体刺激的反应，包括所有三个特征。α受体细胞表现出边缘皱褶和应力纤维的丢失，但在几个独立的α受体细胞系中未发现圆形皱褶。β受体细胞，而不是α受体细胞，能够向配体的浓度梯度迁移。通过比较[32 P]正磷酸盐标记的完整细胞中α和β受体的潜在底物磷酸化增加的模式，并使用体外激酶试验，探索了信号传导差异的分子基础。某些观察到的底物是共同的两种受体，而其他人是特定的。我们得出结论，某些已知的PDGF诱导的细胞效应仅由β受体转导; α受体特异性底物的存在表明也存在α受体特异性信号，尚未确定。
We have examined the signal transduction pathways of the PDGF alpha‐ and beta‐receptors, in order to characterize the specificity of each receptor type in the signaling. Porcine aortic endothelial cell lines expressing equal levels of either PDGF alpha‐ or beta‐receptors were established. The alpha‐ and beta‐receptor cells responded mitogenically to stimulation with the proper PDGF isoforms. Three aspects of actin reorganization were examined after ligand stimulation: loss of stress fibres, appearance of edge ruffles and formation of circular membrane ruffles. The beta‐receptor cells showed a response to ligand stimulation which included all three features. The alpha‐receptor cells exhibited edge ruffles and loss of stress fibres, but circular ruffles could not be found in several independent alpha‐receptor cell lines. The beta‐receptor cells, but not the alpha‐receptor cells, were able to migrate chemotactically towards a concentration gradient of ligand. The molecular basis for the differences in signalling were explored by comparing the pattern of increased phosphorylation of potential substrates for the alpha‐ and beta‐receptors in [32P]orthophosphate labelled intact cells and using an in vitro kinase assay. Certain of the observed substrates were common for the two receptors, whereas others were specific for either one. We conclude that certain of the known PDGF induced cellular effects are transduced only by the beta‐receptor; the presence of alpha‐receptor‐specific substrates suggests that there are also alpha‐receptor‐specific signals, which have yet to be identified.