Kratchmarova Irina, Blagoev Blagoy, Haack-Sorensen Mandana, Kassem Moustapha, Mann Matthias
Center for Experimental BioInformatics (CEBI), Department of Biochemistry and Molecular Biology, University of Southern Denmark, Campusvej 55, DK-5230 Odense M, Denmark.
Science. 2005 Jun 3;308(5727):1472-7. doi: 10.1126/science.1107627.
Closely related signals often lead to very different cellular outcomes. We found that the differentiation of human mesenchymal stem cells into bone-forming cells is stimulated by epidermal growth factor (EGF) but not platelet-derived growth factor (PDGF). We used mass spectrometry-based proteomics to comprehensively compare proteins that were tyrosine phosphorylated in response to EGF and PDGF and their associated partners. More than 90% of these signaling proteins were used by both ligands, whereas the phosphatidylinositol 3-kinase (PI3K) pathway was exclusively activated by PDGF, implicating it as a possible control point. Indeed, chemical inhibition of PI3K in PDGF-stimulated cells removed the differential effect of the two growth factors, bestowing full differentiation effect onto PDGF. Thus, quantitative proteomics can directly compare entire signaling networks and discover critical differences capable of changing cell fate.
密切相关的信号常常导致截然不同的细胞结果。我们发现，表皮生长因子（EGF）能刺激人间充质干细胞分化为成骨细胞，而血小板衍生生长因子（PDGF）则不能。我们使用基于质谱的蛋白质组学方法全面比较了响应EGF和PDGF而发生酪氨酸磷酸化的蛋白质及其相关伴侣。这些信号蛋白中有90%以上被两种配体共同使用，而磷脂酰肌醇3-激酶（PI3K）途径仅由PDGF激活，这表明它可能是一个控制点。事实上，在PDGF刺激的细胞中化学抑制PI3K消除了两种生长因子的差异效应，赋予PDGF完全的分化效应。因此，定量蛋白质组学可以直接比较整个信号网络，并发现能够改变细胞命运的关键差异。
