Fambrough D, McClure K, Kazlauskas A, Lander E S
Whitehead Institute for Biomedical Research, Cambridge, Massachusetts 02142, USA.
Cell. 1999 Jun 11;97(6):727-41. doi: 10.1016/s0092-8674(00)80785-0.
We sought to explore the relationship between receptor tyrosine kinase (RTK) activated signaling pathways and the transcriptional induction of immediate early genes (IEGs). Using global expression monitoring, we identified 66 fibroblast IEGs induced by platelet-derived growth factor beta receptor (PDGFRbeta) signaling. Mutant receptors lacking binding sites for activation of the PLCgamma, PI3K, SHP2, and RasGAP pathways still retain partial ability to induce 64 of these IEGs. Removal of the Grb2-binding site further broadly reduces induction. These results suggest that the diverse pathways exert broadly overlapping effects on IEG induction. Interestingly, a mutant receptor that restores the RasGAP-binding site promotes induction of an independent group of genes, normally induced by interferons. Finally, we compare the PDGFRbeta and fibroblast growth factor receptor 1; each induces essentially identical IEGs in fibroblasts.
我们试图探究受体酪氨酸激酶（RTK）激活的信号通路与即刻早期基因（IEG）转录诱导之间的关系。通过全局表达监测，我们鉴定出66个由血小板衍生生长因子β受体（PDGFRβ）信号诱导的成纤维细胞IEG。缺乏PLCγ、PI3K、SHP2和RasGAP通路激活结合位点的突变受体仍保留诱导其中64个IEG的部分能力。去除Grb2结合位点会进一步广泛降低诱导作用。这些结果表明，多种通路对IEG诱导发挥广泛重叠的作用。有趣的是，一个恢复RasGAP结合位点的突变受体促进了一组通常由干扰素诱导的独立基因的诱导。最后，我们比较了PDGFRβ和成纤维细胞生长因子受体1；它们在成纤维细胞中诱导的IEG基本相同。
