α5β1 Integrin Controls Cyclin D1 Expression by Sustaining Mitogen-activated Protein Kinase Activity in Growth Factor-treated Cells
α5β1 Integrin Controls Cyclin D1 Expression by Sustaining Mitogen-activated Protein Kinase Activity in Growth Factor-treated Cells
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DOI：
10.1091/mbc.10.10.3197
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发表时间：
1999-10
影响因子：
3.3
通讯作者：
K. Roovers;G. Davey;Xiao-yun Zhu;M. Bottazzi;R. Assoian
中科院分区：
文献类型：
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作者：
K. Roovers;G. Davey;Xiao-yun Zhu;M. Bottazzi;R. Assoian
在许多细胞类型中，细胞周期蛋白D1的表达受生长因子和细胞与细胞外基质的黏附共同调节。生长因子被认为调节细胞周期蛋白D1的表达，因为它们刺激持续的细胞外信号调节激酶(ERK)活性。然而，我们在这里表明，当加入悬浮成纤维细胞时，生长因子诱导瞬时ERK活性，而只有当加入贴壁成纤维细胞时，生长因子才会诱导持久的ERK活性。在生长因子处理的细胞中，细胞与纤维连接蛋白或抗α5β1整合素的结合足以维持ERK信号并诱导细胞周期蛋白D1。此外，当我们通过有条件地表达具有结构性活性的MAPK/ERK激酶来强制持续激活ERK时，我们克服了表达Cyclin D1的粘附性要求。因此，至少在一定程度上，成纤维细胞是有丝分裂原和锚定依赖的，因为整合素的作用允许在生长因子处理的细胞中持续的ERK信号和细胞周期蛋白D1的表达。
Cyclin D1 expression is jointly regulated by growth factors and cell adhesion to the extracellular matrix in many cell types. Growth factors are thought to regulate cyclin D1 expression because they stimulate sustained extracellular signal-regulated kinase (ERK) activity. However, we show here that growth factors induce transient ERK activity when added to suspended fibroblasts and sustained ERK activity only when added to adherent fibroblasts. Cell attachment to fibronectin or anti-alpha5beta1 integrin is sufficient to sustain the ERK signal and to induce cyclin D1 in growth factor-treated cells. Moreover, when we force the sustained activation of ERK, by conditional expression of a constitutively active MAP kinase/ERK kinase, we overcome the adhesion requirement for expression of cyclin D1. Thus, at least in part, fibroblasts are mitogen and anchorage dependent, because integrin action allows for a sustained ERK signal and the expression of cyclin D1 in growth factor-treated cells.