Cell adhesion-dependent cofilin serine 3 phosphorylation by the integrin-linked kinase•c-Src complex
Cell adhesion-dependent cofilin serine 3 phosphorylation by the integrin-linked kinase•c-Src complex
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DOI：
10.1074/jbc.m708300200
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发表时间：
2008-04-11
影响因子：
4.8
通讯作者：
Lee, Jung Weon
中科院分区：
文献类型：
--
作者：
Kim, Yong-Bae;Choi, Suyong;Lee, Jung Weon
整合素连接激酶（ILK）参与整合素介导的细胞粘附的信号转导，导致动态肌动蛋白重组。肌动蛋白聚合（去聚合）受cofilin调节，其Ser（3）磷酸化（pS（3）cofilin）抑制其肌动蛋白切断活性。为了确定ILK如何调节pS（3）cofilin，我们使用正常RIE 1细胞检测了ILK对pS（3）cofilin的作用。与悬浮细胞相比，纤连蛋白粘附细胞显示增强的pS（3）cofilin，这取决于ILK表达和c-Src活性。在RIE 1细胞中ILK介导的pS（3）cofilin不涉及Rho相关激酶、LIM激酶或睾丸蛋白激酶，这些激酶已知是cofilin的上游。ILK的激酶结构域，包括富含脯氨酸的区域，似乎与c-Src的Src同源性3结构域物理相互作用。在体外激酶试验表明，ILK免疫沉淀磷酸化的重组谷胱甘肽S-转移酶-cofilin，这是废除c-Src抑制。有趣的是，表皮生长因子处理消除了ILK效应，表明ILK与cofilin的连接对细胞外信号具有生物学响应。总之，这项研究提供了一个新的信号连接ILK的cofilin动态肌动蛋白聚合在细胞粘附过程中，根据ILK相关的c-Src的活性的证据。
Integrin- linked kinase (ILK) is involved in signal transduction by integrin-mediated cell adhesion that leads to dynamic actin reorganization. Actin (de) polymerization is regulated by cofilin, the Ser(3) phosphorylation (pS(3) cofilin) of which inhibits its actin-severing activity. To determine how ILK regulates pS(3) cofilin, we examined the effects of ILK on pS(3) cofilin using normal RIE1 cells. Compared with suspended cells, fibronectin-adherent cells showed enhanced pS(3) cofilin, depending on ILK expression and c-Src activity. The ILK-mediated pS(3) cofilin in RIE1 cells did not involve Rho-associated kinase, LIM kinase, or testicular protein kinases, which are known to be upstream of cofilin. The kinase domain of ILK, including proline-rich regions, appeared to interact physically with the Src homology 3 domain of c-Src. In vitro kinase assay revealed that ILK immunoprecipitates phosphorylated the recombinant glutathione S-transferase-cofilin, which was abolished by c-Src inhibition. Interestingly, epidermal growth factor treatment abolished the ILK effects, indicating that the linkage from ILK to cofilin is biologically responsive to extracellular cues. Altogether, this study provides evidence for a new signaling connection from ILK to cofilin for dynamic actin polymerization during cell adhesion, depending on the activity of ILK-associated c-Src.