THE ALPHA-5-BETA-1 INTEGRIN SUPPORTS SURVIVAL OF CELLS ON FIBRONECTIN AND UP-REGULATES BCL-2 EXPRESSION
THE ALPHA-5-BETA-1 INTEGRIN SUPPORTS SURVIVAL OF CELLS ON FIBRONECTIN AND UP-REGULATES BCL-2 EXPRESSION
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DOI：
10.1073/pnas.92.13.6161
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发表时间：
1995-06-20
影响因子：
11.1
通讯作者：
RUOSLAHTI, E
中科院分区：
文献类型：
--
作者：
ZHANG, ZH;VUORI, K;RUOSLAHTI, E
被阻止附着于细胞外基质的锚定依赖性细胞停止增殖并可能经历凋亡。细胞与基质的粘附是由细胞表面受体的整联蛋白家族介导的，已知其在细胞粘附时引发细胞内信号。我们在此表明，表达α v β 1整联蛋白（其是一种纤连蛋白受体）的中国仓鼠卵巢细胞在将细胞接种在纤连蛋白上时，在血清撤除后不发生凋亡。然而，α v β 1整联蛋白，其也是一种纤连蛋白受体，并在与α 5 β 1相同的RGD基序上结合纤连蛋白，不能阻止相同细胞在纤连蛋白上的凋亡。整合素α 5亚基的胞质结构域是α 5 β 1介导的细胞在纤连蛋白上存活所必需的，纤连蛋白介导的存活效应似乎不依赖于粘着斑激酶的酪氨酸磷酸化水平，粘着斑激酶由整合素介导的细胞粘附诱导。Bcl-2蛋白的表达，其对抗细胞凋亡，在通过α 5 β 1附着于纤连蛋白的细胞中，α v β 1的表达水平升高;通过α v β 1附着的细胞只有在提供外源性Bcl-2时才存活。因此，α 5 β 1，而不是密切相关的α v β 1整联蛋白，似乎通过Bcl-2途径抑制凋亡性细胞死亡。
Anchorage dependent cells that are prevented from attaching to an extracellular matrix substrate stop proliferating and may undergo apoptosis. Cell adhesion to a substrate is mediated by the integrin family of cell surface receptors, which are known to elicit intracellular signals upon cell adhesion, We show here that Chinese hamster ovary cells expressing the alpha 5 beta 1 integrin, which is a fibronectin receptor, do not undergo apoptosis upon serum withdrawal when the cells are plated on fibronectin, However, the alpha v beta 1 integrin, which is also a fibronectin receptor and binds fibronectin on the same RGD motif as alpha 5 beta 1, did not prevent apoptosis on fibronectin of the same cells, The cytoplasmic domain of the integrin alpha 5 subunit was required for the alpha 5 beta 1-mediated cell survival on fibronectin, The fibronectin-mediated survival effect appeared to be independent of the level of tyrosine phosphorylation of the focal adhesion kinase, which is induced by integrin-mediated cell attachment, The expression of the Bcl-2 protein, which counteracts apoptosis, was elevated in cells attaching to fibronectin through alpha 5 beta 1; cells attaching through alpha v beta 1 survived only if exogenous Bcl-2 was provided, Thus, alpha 5 beta 1, but not the closely related alpha v beta 1 integrin, appears to suppress apoptotic cell death through the Bcl-2 pathway.