Proteomic analysis of integrin-associated complexes identifies RCC2 as a dual regulator of Rac1 and Arf6.
Proteomic analysis of integrin-associated complexes identifies RCC2 as a dual regulator of Rac1 and Arf6.
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DOI：
10.1126/scisignal.2000396
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发表时间：
2009-09-08
影响因子：
7.3
通讯作者：
Humphries MJ
中科院分区：
文献类型：
--
作者：
Humphries JD;Byron A;Bass MD;Craig SE;Pinney JW;Knight D;Humphries MJ
整合素粘附受体与其细胞外基质配体的结合控制细胞形态、运动、存活和各种发育、稳态和疾病过程中的分化。在这里，我们报告了一种方法来分离与整合素粘附受体，其中，像其他受体相关的信号复合物，已难蛋白质组学分析相关的复合物。对两种受体-配体对α4β1-VCAM-1和α5β1-纤连蛋白的蛋白质组进行定量比较分析，确定了核心和受体特异性组分。在Rac 1和Arf 6子网络之间的交叉点处的α5β1-纤连蛋白信号网络中检测到染色体凝聚调节因子2（RCC 2）。RCC 2敲低增强了纤连蛋白诱导的Rac 1和Arf 6的激活，并加速了细胞铺展，这表明RCC 2限制了膜突起和递送所需的信号传导。RCC 2敲低导致Rac 1和Arf 6功能失调，也消除了沿纤连蛋白纤维的持续迁移沿着，表明RCC 2在定向细胞运动中的功能作用。这种蛋白质组学工作流程现在为进一步解剖和系统水平分析粘附信号开辟了道路。
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, α4β1–VCAM-1 and α5β1–fibronectin, defined both core and receptor-specific components. Regulator of chromosome condensation-2 (RCC2) was detected in the α5β1–fibronectin signaling network at an intersection between the Rac1 and Arf6 sub-networks. 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.
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影响因子：
4
作者：
Humphries JD;Byron A;Humphries MJ
通讯作者：
Humphries MJ
影响因子：
7.5
作者：
Delon, Isabelle;Brown, Nicholas H.
通讯作者：
Brown, Nicholas H.
影响因子：
64.5
作者：
de Hoog, CL;Foster, LJ;Mann, M
通讯作者：
Mann, M
影响因子：
3.2
作者：
Bellissent-Waydelich, A;Vanier, MT;Simon-Assmann, P
通讯作者：
Simon-Assmann, P
DOI：
10.1073/pnas.0409513102
发表时间：
2005-06-28
影响因子：
11.1
作者：
Gorrini, C;Loreni, F;Biffo, S
通讯作者：
Biffo, S