Downregulation of platelet-derived growth factor receptor-β in Shp-2 mutant fibroblast cell lines
Downregulation of platelet-derived growth factor receptor-β in Shp-2 mutant fibroblast cell lines
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DOI：
10.1038/sj.onc.1201988
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发表时间：
1998-07-30
期刊：
影响因子：
8
通讯作者：
Feng, GS
中科院分区：
文献类型：
--
作者：
Lu, XL;Qu, CK;Feng, GS
含有sh2的酪氨酸磷酸酶Shp-2似乎在多种生长因子受体的下游发挥作用，并可能在细胞增殖中发挥积极作用。本文报道，在缺乏Shp-2功能的突变型成纤维细胞中，血小板衍生生长因子受体（pdgfr - β）的β亚基表达特异性下调，而pdgfr - α EGFR和IGFIR的水平没有改变。pdgf刺激的DNA合成和细胞外信号调节激酶（Erk）的激活在突变细胞中受到严重抑制，在pdgf处理后，突变细胞中的酪氨酸上没有磷酸化响应pdgfr - β而不响应pdgfr - α的RasGAP， Northern blot分析未能检测到突变细胞中的pdgfr - β mRNA。在Shp-2突变细胞中，pdgfr - β基因启动子的转录起始没有明显改变，但其mRNA的半衰期缩短。这些观察结果表明，Shp-2不仅参与生长因子受体信号的传递，而且在控制pdgfr - β表达中起着特定的作用。我们认为这是Shp-2正向调控细胞增殖的重要机制。
The SH2-containing tyrosine phosphatase Shp-2 appears to function downstream of a variety of growth factor receptors and might play a positive role in cell proliferation, Here we report that expression of the beta subunit of platelet-derived growth factor receptor (PDGFR-beta) was specifically downregulated in mutant fibroblasts lacking a functional Shp-2, while the levels of PDGFR-alpha EGFR and IGFIR were not changed, PDGF-stimulated DNA synthesis and extracellular signal regulated kinase (Erk) activation was severely suppressed in mutant cells, RasGAP, that responds to activation of PDGFR-beta but not PDGFR-alpha, was not phosphorylated on tyrosine in mutant cells upon PDGF-treatment, Northern blot analysis failed to detect PDGFR-beta mRNA in mutant cells. The transcription initiation from the PDGFR-beta gene promoter was not significantly changed, but the half-life of its mRNA was shortened in Shp-2 mutant cells. These observations indicate that Shp-2 not only participates in transmission of signals from growth factor receptors but also plays a specific role in the control of the PDGFR-beta expression. We propose that this is an important mechanism for the positive control of cell proliferation by Shp-2.