Two-stage activation for α5β1 integrin binding to surface-adsorbed fibronectin
Two-stage activation for α5β1 integrin binding to surface-adsorbed fibronectin
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DOI：
10.1074/jbc.273.52.34710
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发表时间：
1998-12-25
影响因子：
4.8
通讯作者：
Boettiger, D
中科院分区：
文献类型：
--
作者：
García, AJ;Takagi, J;Boettiger, D
通过分析完整细胞中α(5)β(1)整合素与吸附纤连蛋白的功能结合，我们证明整合素激活导致粘附强度线性增加，作为配体密度的函数，这表明受体-配体相互作用的调节是粘附初始阶段粘附的主要机制，并且协同结合对初始粘附强度贡献很小。使用这个实验框架，我们证明了α(5)β(1)整合素与吸附的纤连蛋白结合存在三种不同的激活状态，包括被动的、抗体诱导的和主动的、细胞控制的激活。在粘附的初始阶段，α(5)β(1) 整联蛋白在能量依赖性过程中被激活，从非结合基态到受体结合纤连蛋白并提供显着机械耦合的中间状态。在粘附成熟的后期阶段，α(5)β(1) 整合素被激活至更高的结合状态，与中间状态相比，粘附强度显着增加。这些多重结合状态很可能是由不同的整联蛋白构象引起的，反映了α(5)β(1)和吸附的纤连蛋白位点之间不同的相互作用。α(5)β(1)的多种激活状态表明粘附信号传导和强化中存在不同的阶段，并且可以为粘附相互作用的调节提供通用机制。
By analyzing the functional binding of alpha(5)beta(1) integrin to adsorbed fibronectin in intact cells, we demonstrate that integrin activation results in linear increases in adhesion strength as a function of ligand density, suggesting that modulation of the receptor-ligand interaction is the dominant mechanism for adhesion during the initial stages of adhesion and that cooperative binding contributes little to initial adhesion strength. Using this experimental framework, we show the existence of three distinct activation states for alpha(5)beta(1) integrin binding to adsorbed fibronectin for both passive, antibody-induced and active, cell-controlled activation. During the initial phase of adhesion, alpha(5)beta(1) integrin is activated in an energy-dependent process from the nonbinding ground state to an intermediate state in which the receptor binds fibronectin and provides significant mechanical coupling. In later stages of adhesion maturation, alpha(5)beta(1) integrin is activated to a higher binding state, which provides significant increases in adhesion strength compared with the intermediate state. These multiple binding states most likely result from different integrin conformations and reflect distinct interactions between alpha(5)beta(1) and sites on adsorbed fibronectin, Multiple activation states for alpha(5)beta(1) suggest the existence of distinct stages in adhesion signaling and strengthening and can provide a versatile mechanism for the regulation of adhesive interactions.