Department of Bioinformatics and Computational Biology, Genentech, Inc., South San Francisco, California 94080, USA.
Mol Cell Proteomics. 2013 Aug;12(8):2070-80. doi: 10.1074/mcp.M112.027052. Epub 2013 Apr 22.
Although K-Ras, Cdc42, and PAK4 signaling are commonly deregulated in cancer, only a few studies have sought to comprehensively examine the spectrum of phosphorylation-mediated signaling downstream of each of these key signaling nodes. In this study, we completed a label-free quantitative analysis of oncogenic K-Ras, activated Cdc42, and PAK4-mediated phosphorylation signaling, and report relative quantitation of 2152 phosphorylated peptides on 1062 proteins. We define the overlap in phosphopeptides regulated by K-Ras, Cdc42, and PAK4, and find that perturbation of these signaling components affects phosphoproteins associated with microtubule depolymerization, cytoskeletal organization, and the cell cycle. These findings provide a resource for future studies to characterize novel targets of oncogenic K-Ras signaling and validate biomarkers of PAK4 inhibition.
虽然 K-Ras、Cdc42 和 PAK4 信号在癌症中经常失调，但只有少数研究试图全面检查这些关键信号节点下游磷酸化介导信号的范围。在这项研究中，我们完成了对致癌 K-Ras、激活的 Cdc42 和 PAK4 介导的磷酸化信号的无标记定量分析，并报告了 1062 种蛋白质上 2152 个磷酸化肽的相对定量。我们定义了 K-Ras、Cdc42 和 PAK4 调节的磷酸肽的重叠，并发现这些信号成分的干扰会影响与微管解聚、细胞骨架组织和细胞周期相关的磷酸蛋白。这些发现为未来的研究提供了一个资源，以表征致癌 K-Ras 信号的新靶标，并验证 PAK4 抑制的生物标志物。
