SH3 domain of spectrin participates in the. activation of Rac in specialized calpain-induced integrin signaling complexes
SH3 domain of spectrin participates in the. activation of Rac in specialized calpain-induced integrin signaling complexes
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DOI：
10.1242/jcs.01625
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发表时间：
2005-01-15
影响因子：
4
通讯作者：
Fox, JEB
中科院分区：
文献类型：
--
作者：
Bialkowska, K;Saido, TC;Fox, JEB
在这项研究中，我们使用生长在Beta3整合素底物上的培养细胞来检测SPECTIN参与信号转导的可能性。血影蛋白与钙蛋白酶诱导的Beta3整合素信号复合体聚集在一起，该复合体介导细胞的初始附着，并启动RAC激活和板脂扩张。在斑块复合体和斑块粘连中不存在，这两种整合素复合体在片状脂膜和完全铺展的细胞中介导粘连。血影蛋白含有一个未知功能的Src同源(SH3)结构域。过度表达该结构域的细胞黏附在一起，形成了由Calain诱导的整合素信号复合体。但抑制RAC激活、片状脂体伸展和细胞铺展。通过过度表达构成活性的RAC来恢复扩散。这些研究指出，在启动细胞黏附和扩散的专门化整合素簇中，血影蛋白及其SH3结构域在启动RAC激活方面的作用以前不为人知。因此，血影蛋白可能在启动整合素诱导的生理和病理事件中发挥关键作用，如发育、增殖、细胞存活、伤口愈合、转移和动脉粥样硬化。
In this study, we used cultured cells spreading on beta3 integrin substrates to examine the possibility that spectrin is involved in signal transduction. Spectrin clustered with specialized calpain-induced beta3 integrin signaling complexes that mediate the initial attachment of cells and initiate Rac activation and lamellipodia extension. It was absent from focal complexes and focal adhesions, the integrin complexes that mediate adhesion in lamellipodia and fully spread cells. Spectrin contains a Src homology (SH3) domain of unknown function. Cells overexpressing this domain adhered and calpain-induced integrin signaling complexes formed. However, Rac activation, lamellipodia extension and cell spreading were inhibited. Spreading was restored by overexpression of constitutively active Rac. These studies point to a previously unrecognized role for spectrin and its SH3 domain in initiating Rac activation in the specialized integrin clusters that initiate cell adhesion and spreading. Thus, spectrin may have a pivotal role in initiating integrin-induced physiological and pathological events such as development, proliferation, cell survival, wound healing, metastasis and atherosclerosis.