科學(xué)家早已知道,，細(xì)胞之間會(huì)通過(guò)一種稱作“信號(hào)傳導(dǎo)”的復(fù)雜過(guò)程進(jìn)行“交談”。當(dāng)這些信號(hào)出現(xiàn)差錯(cuò),，就可能導(dǎo)致糖尿病,、關(guān)節(jié)炎以及癌癥等多種疾病?？茖W(xué)家目前對(duì)于發(fā)生于細(xì)胞膜上的信號(hào)傳收情況已經(jīng)進(jìn)行了大量的研究,，但是對(duì)于進(jìn)入膜后的情況卻知之甚少。結(jié)果,，對(duì)于市場(chǎng)上的許多藥物,，科學(xué)家并不是十分清楚它們對(duì)于細(xì)胞功能所具有的影響。
英國(guó)曼徹斯特大學(xué)的科學(xué)家近日開(kāi)發(fā)出一種新技術(shù),，將能幫助科學(xué)家理解這些信號(hào)如何通過(guò)細(xì)胞膜進(jìn)入細(xì)胞內(nèi)部,，并觸發(fā)一系列復(fù)雜的生物學(xué)過(guò)程。相關(guān)論文發(fā)表在《科學(xué)—信號(hào)傳導(dǎo)》（Science Signaling）上,。
論文通訊作者,、曼徹斯特大學(xué)生命科學(xué)系系主任Martin Humphries教授說(shuō)：“信號(hào)讓細(xì)胞以一種類似于我們品嘗食物和水的方式來(lái)‘品嘗’環(huán)境。就像紅葡萄酒有多種不同的微妙的味道一樣,，細(xì)胞也能‘嘗’到構(gòu)成其環(huán)境的數(shù)千種分子,。我們的發(fā)現(xiàn)解釋了細(xì)胞如何在分子水平上闡釋這些不同的味道，從而產(chǎn)生一個(gè)總體的信號(hào),。我們開(kāi)發(fā)的技術(shù)將幫助科學(xué)家檢測(cè)細(xì)胞表面受體如何將信息傳給細(xì)胞內(nèi)數(shù)百種蛋白,。特別是,，它將能幫助科學(xué)家同時(shí)關(guān)注所有這些組分。”
這項(xiàng)研究將會(huì)在科學(xué)界激起強(qiáng)烈的興趣,，有望導(dǎo)致更好的藥物設(shè)計(jì)和更快的藥物遞送時(shí)間,。此外，它還將幫助科學(xué)家更全面地認(rèn)識(shí)我們的身體機(jī)能,。（生物谷Bioon.com）
生物谷推薦原始出處：
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.
