Integrins in invasive growth
Integrins in invasive growth
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DOI：
10.1172/jci200215468
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发表时间：
2002-04-01
影响因子：
15.9
通讯作者：
Fässler, R
中科院分区：
文献类型：
--
作者：
Brakebusch, C;Bouvard, D;Fässler, R
J. Clin. Invest. 109：999-1006（2002）。DOI：10.1172/JCI 200215468。它们参与整联蛋白亲和力的调节。这种调节的潜在候选者是ICAP-1和TAP-20，其降低，以及β3-内切蛋白，其增加过表达这些分子的细胞中整合素介导的粘附。细胞内信号传导机制，例如CaMKII对ICAP-1的磷酸化，被认为调节这些分子与整联蛋白的结合，从而调节亲和力状态。细胞粘附不仅可以通过亲和力调节来诱导，而且可以通过整合素的聚集来诱导，这导致粘附亲合力增加。这种簇存在于粘着斑中，粘着斑是容易检测到的细胞基质接触，在培养的成纤维细胞中已被广泛研究。整合素在膜中的横向移动性增加对于有效的配体结合也可能是重要的。在白细胞中，甚至在配体结合之前，整联蛋白似乎与肌动蛋白网络相关，这限制了整联蛋白的移动性和配体结合。通过整合素与细胞骨架连接的蛋白水解消化释放这种接触，导致整合素的侧向移动性迅速增加，这增加了配体相遇的机会，并促进整合素聚集成高亲合力簇（4）。
J. Clin. Invest. 109: 999–1006 (2002). DOI: 10.1172/JCI200215468. them are involved in the modulation of integrin affinity. Potential candidates for such regulation are ICAP-1 and TAP-20, which decrease, and β3-endonexin, which increases integrin-mediated adhesion in cells overexpressing these molecules. Intracellular signaling mechanisms, for example phosphorylation of ICAP-1 by CaMKII, are suggested to modulate the binding of these molecules to integrin and thereby the affinity state. Cell attachment can be induced not only by affinity regulation, but also by clustering of integrins, which leads to increased adhesive avidity. Such clusters are present in focal adhesions, readily detectable cellmatrix contacts that have been extensively studied in cultured fibroblasts. Increased lateral mobility of integrins in the membrane might also be important for efficient ligand binding. In leukocytes, even prior to ligand binding, integrins seem to be associated with the actin network, which constrains integrin mobility and ligand binding. Releasing this contact by proteolytic digestion of the integrin connections with the cytoskeleton results in a rapid increase in lateral mobility of integrins, which increases the chance of ligand encounters and facilitates integrin aggregation into high-avidity clusters (4).