Activation of αvβ3-vitronectin binding is a multistage process in which increases in bond strength are dependent on Y747 and Y759 in the cytoplasmic domain of β3
Activation of αvβ3-vitronectin binding is a multistage process in which increases in bond strength are dependent on Y747 and Y759 in the cytoplasmic domain of β3
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DOI：
10.1091/mbc.12.5.1227
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发表时间：
2001-05-01
影响因子：
3.3
通讯作者：
Blystone, S
中科院分区：
文献类型：
--
作者：
Boettiger, D;Huber, F;Blystone, S
整合素受体作为细胞与其结构环境之间的机械连接。使用在K562细胞中表达的α（v）β 3整联蛋白作为模型系统，通过测量这些键对机械分离的抗性来分析α（v）β 3和玻连蛋白之间的机械连接发展的过程。通过突变、生物化学和生物力学分析，定义了三个不同的激活阶段，定义为α（v）β 3-玻连蛋白结合强度的增加。通过与玻连蛋白配体的相互作用激活至低结合强度阶段1，并导致β 3亚基中Y 747的磷酸化。第2阶段的特征在于结合强度增加4倍，并且依赖于第1阶段和Y 747的磷酸化。第3阶段的特征在于结合强度进一步增加2.5倍，并且依赖于第2阶段事件和Y 759与细胞蛋白相互作用的可用性。Y 747 F突变体阻断了从第I阶段到第2阶段的转变，Y 759 F阻断了从第2阶段到第3阶段的转变。这些数据表明了α（V）β 3整合素张力诱导活化的模型。
Integrin receptors serve as mechanical links between the cell and its structural environment. Using alpha (v)beta3 integrin expressed in K562 cells as a model system, the process by which the mechanical connection between alpha (v)beta3 and vitronectin develops was analyzed by measuring the resistance of these bonds to mechanical separation. Three distinct stages of activation, as defined by increases in the alpha (v)beta3-vitronectin binding strength, were defined by mutational, biochemical, and biomechanical analyses. Activation to the low binding strength stage 1 occurs through interaction with the vitronectin ligand and leads to the phosphorylation of Y747 in the beta3 subunit. Stage 2 is characterized by a 4-fold increase in binding strength and is dependent on stage 1 and the phosphorylation of Y747. Stage 3 is characterized by a further 2.5-fold increase in binding strength and is dependent on stage 2 events and the availability of Y759 for interaction with cellular proteins. The Y747F mutant blocked the transition from stage I to stage 2, and the Y759F blocked the transition from stage 2 to stage 3. The data suggest a model for tension-induced activation of alpha (v)beta3 integrin.