科学家早已知道，细胞之间会通过一种称作“信号传导”的复杂过程进行“交谈”。当这些信号出现差错，就可能导致糖尿病、关节炎以及癌症等多种疾病。科学家目前对于发生于细胞膜上的信号传收情况已经进行了大量的研究，但是对于进入膜后的情况却知之甚少。结果，对于市场上的许多药物，科学家并不是十分清楚它们对于细胞功能所具有的影响。
英国曼彻斯特大学的科学家近日开发出一种新技术，将能帮助科学家理解这些信号如何通过细胞膜进入细胞内部，并触发一系列复杂的生物学过程。相关论文发表在《科学—信号传导》（Science Signaling）上。
论文通讯作者、曼彻斯特大学生命科学系系主任Martin Humphries教授说：“信号让细胞以一种类似于我们品尝食物和水的方式来‘品尝’环境。就像红葡萄酒有多种不同的微妙的味道一样，细胞也能‘尝’到构成其环境的数千种分子。我们的发现解释了细胞如何在分子水平上阐释这些不同的味道，从而产生一个总体的信号。我们开发的技术将帮助科学家检测细胞表面受体如何将信息传给细胞内数百种蛋白。特别是，它将能帮助科学家同时关注所有这些组分。”
这项研究将会在科学界激起强烈的兴趣，有望导致更好的药物设计和更快的药物递送时间。此外，它还将帮助科学家更全面地认识我们的身体机能。（生物谷Bioon.com）
生物谷推荐原始出处：
Sci. Signal., 8 September 2009 DOI: 10.1126/scisignal.2000396
Proteomic Analysis of Integrin-Associated Complexes Identifies RCC2 as a Dual Regulator of Rac1 and Arf6
Jonathan D. Humphries1,2*, Adam Byron1,2*, Mark D. Bass1,2, Sue E. Craig1,2, John W. Pinney2, David Knight2, and Martin J. Humphries1,2
1 Wellcome Trust Centre for Cell-Matrix Research, University of Manchester, Manchester M13 9PT, UK.
2 Faculty of Life Sciences, University of Manchester, Manchester M13 9PT, UK.
* These authors contributed equally to this work.
Present address: Centre for Bioinformatics, Division of Molecular Biosciences, Imperial College London, London SW7 2AZ, UK.
Abstract: The binding of integrin adhesion receptors to their extracellular matrix ligands controls cell morphology, movement, survival, and differentiation in various developmental, homeostatic, and disease processes. Here, we report a methodology to isolate complexes associated with integrin adhesion receptors, which, like other receptor-associated signaling complexes, have been refractory to proteomic analysis. Quantitative, comparative analyses of the proteomes of two receptor-ligand pairs, 4β1–vascular cell adhesion molecule–1 and 5β1–fibronectin, defined both core and receptor-specific components. Regulator of chromosome condensation–2 (RCC2) was detected in the 5β1–fibronectin signaling network at an intersection between the Rac1 and adenosine 5'-diphosphate ribosylation factor 6 (Arf6) subnetworks. RCC2 knockdown enhanced fibronectin-induced activation of both Rac1 and Arf6 and accelerated cell spreading, suggesting that RCC2 limits the signaling required for membrane protrusion and delivery. Dysregulation of Rac1 and Arf6 function by RCC2 knockdown also abolished persistent migration along fibronectin fibers, indicating a functional role for RCC2 in directional cell movement. This proteomics workflow now opens the way to further dissection and systems-level analyses of adhesion signaling.
