Wang Yingchun, Ding Shi-Jian, Wang Wei, Jacobs Jon M, Qian Wei-Jun, Moore Ronald J, Yang Feng, Camp David G, Smith Richard D, Klemke Richard L
Department of Pathology and Moores Cancer Center, University of California at San Diego, La Jolla, CA 92093, USA.
Proc Natl Acad Sci U S A. 2007 May 15;104(20):8328-33. doi: 10.1073/pnas.0701103104. Epub 2007 May 9.
Cell movement requires morphological polarization characterized by formation of a leading pseudopodium (PD) at the front and a trailing rear at the back. However, little is known about how protein networks are spatially integrated to regulate this process at the system level. Here, we apply global proteome profiling in combination with newly developed quantitative phosphoproteomics approaches for comparative analysis of the cell body (CB) and PD proteome of chemotactic cells. The spatial relationship of 3,509 proteins and 228 distinct sites of phosphorylation were mapped revealing networks of signaling proteins that partition to the PD and/or the CB compartments. The major network represented in the PD includes integrin signaling, actin regulatory, and axon guidance proteins, whereas the CB consists of DNA/RNA metabolism, cell cycle regulation, and structural maintenance. Our findings provide insight into the spatial organization of signaling networks that control cell movement and provide a comprehensive system-wide profile of proteins and phosphorylation sites that control cell polarization.
细胞运动需要形态极化，其特征是在前端形成一个领先的伪足（PD），在后端形成一个拖尾的后部。然而，关于蛋白质网络如何在系统水平上进行空间整合以调节这一过程，我们所知甚少。在这里，我们应用全局蛋白质组分析，并结合新开发的定量磷酸蛋白质组学方法，对趋化细胞的细胞体（CB）和PD蛋白质组进行比较分析。绘制了3509种蛋白质和228个不同磷酸化位点的空间关系，揭示了分配到PD和/或CB区室的信号蛋白网络。PD中代表的主要网络包括整合素信号传导、肌动蛋白调节和轴突导向蛋白，而CB则由DNA/RNA代谢、细胞周期调节和结构维持组成。我们的研究结果为控制细胞运动的信号网络的空间组织提供了见解，并提供了控制细胞极化的蛋白质和磷酸化位点的全面全系统概况。
