Emerging role of ILK and ELMO2 in the integration of adhesion and migration pathways

Emerging role of ILK and ELMO2 in the integration of adhesion and migration pathways
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DOI:
10.4161/cam.20399
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发表时间:
2012-05-01
影响因子:
3.2
通讯作者:
Dagnino, Lina
Dagnino, Lina
中科院分区:
生物学3区
文献类型:
--
作者:
Ho, Ernest;Dagnino, Lina

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整合素及其相关蛋白是调节粘附和迁移的细胞机制的重要组成部分。特别地,与β 1整联蛋白的胞质尾区结合的整联蛋白连接激酶(ILK)是多种细胞类型中的迁移所需的。我们以前确定的吞噬和运动2(ELMO 2)作为ILK结合蛋白在表皮角质形成细胞。最近,我们研究了ILK/ELMO 2复合物的生物学作用,发现它们存在于细胞质中。ILK/ELMO 2物种被活性RhoG募集到质膜,在那里它们诱导Rac 1活化并在迁移细胞的前缘形成片状伪足。大量的生长因子和细胞因子诱导角质形成细胞迁移。然而,我们发现RhoG/ELMO 2/ILK复合物的形成选择性地发生在表皮生长因子的刺激下,而不是通过转化生长因子β 1或角质形成细胞生长因子。在这里,我们讨论了这些复合物的相关性,我们了解的分子机制参与细胞迁移,以及它们的潜在功能,在损伤后的形态发生和组织再生。
Integrins and their associated proteins are essential components of the cellular machinery that modulates adhesion and migration. In particular, integrin-linked kinase (ILK), which binds to the cytoplasmic tail of beta 1 integrins, is required for migration in a variety of cell types. We previously identified engulfment and motility 2 (ELMO2) as an ILK-binding protein in epidermal keratinocytes. Recently, we investigated the biological role of the ILK/ELMO2 complexes, and found that they exist in the cytoplasm. ILK/ELMO2 species are recruited by active RhoG to the plasma membrane, where they induce Rac1 activation and formation of lamellipodia at the leading edge of migrating cells. A large number of growth factors and cytokines induce keratinocyte migration. However, we found that formation of RhoG/ELMO2/ILK complexes occurs selectively upon stimulation by epidermal growth factor, but not by transforming growth factor-beta 1 or keratinocyte growth factor. Herein we discuss the relevance of these complexes to our understanding of the molecular mechanisms involved in cell migration, as well as their potential functions in morphogenesis and tissue regeneration following injury.