Signal transduction through cell surface receptors

虽然可以通过整合素及其配体的表达调节粘附，但在不改变表达水平的情况下，整合素也可以介导粘附。这种对附着力的调节称为亲和度调制。骨髓来源的肥大细胞仅通过PMA、steel因子或与FceRI交联刺激的vla5粘附在纤维连接蛋白上，而vla5的表达水平没有变化。整合素的亲和力调节可以通过整合素分子的空间重新分布或对配体的亲和力变化来实现。首先，我们分析了整合素VLA-5在有或没有这些刺激的情况下的形态学变化和亚细胞定位。无刺激时，VLA-5呈簇状分布在细胞体上。SLF和PMA刺激，而非FceRI刺激，可诱导皱褶样膜结构和位于细胞体和皱褶样结构上的vla5的弥漫性分布。在未受刺激的肥大细胞中，VLA-5对80 kD纤维连接蛋白片段的亲和力超出了可检测水平。FceRI交联刺激增加了vla5的亲和力，而SLF或PMA则没有。因此，SLF和PMA主要调节的是vla5分子的空间组织，而FceRI调节的是vla5对纤维连接蛋白的亲和力。这些结果表明，不同的刺激对肥大细胞上VLA-5的空间组织有不同的调节。

Although adhesion can be regulated by the expression of integrin and its igand, adhesion can be also mediated by integrin without any change of the expression level. This regulation of adhesion is called avidity modulation. Bone-marrow derived mast cells adhere to fibronectin via VLA-5 only stimulated with PMA,steel factor, or crosslinking with FceRI without any change of expression levels of VLA-5. Avidity modulation of integrin can be brought by either spatial redistribution of integrin molecules or a change of affinity for a ligand.First we analyzed morphological changes and subcellulare localization of integrin VLA-5 with or without these stimuli. Without stimuli, VLA-5 were distributed as a cluster on the cell body. Stimulation with SLF and PMA,but not FceRI induced ruffle-like membrane structures and diffused distribution of VLA-5, which was located on both the cell body and ruffle-like structures. The affinity of VLA-5 against a 80 kD fibronectin fragment is beyond detectable levels in unstimulated mast cells. Stimulation with crosslinking of FceRI,but not with SLF or PMA increased the affinity of VLA-5. Therefore, SLF and PMA modulate mainly a spatial organization of VLA-5 molecules, while FceRI modulates the affinity of VLA-5 against fibronectin. These results suggest that spatial organization of VLA-5 on mast cells were differentially regulated with distinct stimuli.