Integrin-mediated adhesion regulates ERK nuclear translocation and phosphorylation of Elk-1.
Integrin-mediated adhesion regulates ERK nuclear translocation and phosphorylation of Elk-1.
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DOI：
10.1083/jcb.153.2.273
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发表时间：
2001-04-16
影响因子：
7.8
通讯作者：
Juliano, R L
中科院分区：
文献类型：
--
作者：
Aplin, A E;Stewart, S A;Assoian, R K;Juliano, R L
整合素介导的与细胞外基质的粘附允许生长因子介导的细胞外信号调节激酶（ERK）的有效活化。调节点已定位于受体磷酸化水平或下游组分Raf和MEK（促分裂原活化蛋白激酶/ERK激酶）的活化。然而，它也是公认的ERK易位从细胞质到细胞核所需的G1期细胞周期的进展。在这里，我们表明，磷酸化的细胞外信号调节激酶的底物，埃尔克-1丝氨酸383，是锚定依赖于生长因子治疗NIH 3 T3成纤维细胞。此外，当我们通过表达ERK级联反应的活性成分激活非粘附细胞中的ERK时，与粘附细胞相比，随后的Elk-1丝氨酸383磷酸化和Elk-1介导的反式激活仍然受损。Elk-1磷酸化依赖于一个完整的肌动蛋白细胞骨架，识别与细胞松弛素D（CCD）治疗。最后，活性MEK的表达未能主要定位ERK的细胞核悬浮细胞或贴壁细胞CCD处理。这些数据表明，整联蛋白介导的肌动蛋白细胞骨架的组织调节激活的ERK的定位，并反过来调节ERK有效磷酸化核底物的能力。
Integrin-mediated adhesion to the extracellular matrix permits efficient growth factor-mediated activation of extracellular signal–regulated kinases (ERKs). Points of regulation have been localized to the level of receptor phosphorylation or to activation of the downstream components, Raf and MEK (mitogen-activated protein kinase/ERK kinase). However, it is also well established that ERK translocation from the cytoplasm to the nucleus is required for G1 phase cell cycle progression. Here we show that phosphorylation of the nuclear ERK substrate, Elk-1 at serine 383, is anchorage dependent in response to growth factor treatment of NIH 3T3 fibroblasts. Furthermore, when we activated ERK in nonadherent cells by expression of active components of the ERK cascade, subsequent phosphorylation of Elk-1 at serine 383 and Elk-1–mediated transactivation were still impaired compared with adherent cells. Elk-1 phosphorylation was dependent on an intact actin cytoskeleton, as discerned by treatment with cytochalasin D (CCD). Finally, expression of active MEK failed to predominantly localize ERK to the nucleus in suspended cells or adherent cells treated with CCD. These data show that integrin-mediated organization of the actin cytoskeleton regulates localization of activated ERK, and in turn the ability of ERK to efficiently phosphorylate nuclear substrates.