Zhang Z, Vuori K, Reed J C, Ruoslahti E
Cancer Research Center, La Jolla Cancer Research Foundation, CA 92037, USA.
Proc Natl Acad Sci U S A. 1995 Jun 20;92(13):6161-5. doi: 10.1073/pnas.92.13.6161.
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.
无法附着于细胞外基质底物的贴壁依赖性细胞会停止增殖，并可能发生凋亡。细胞与底物的黏附由细胞表面受体整合素家族介导，已知这些受体在细胞黏附时会引发细胞内信号。我们在此表明，表达α5β1整合素（一种纤连蛋白受体）的中国仓鼠卵巢细胞，当接种在纤连蛋白上时，血清撤除后不会发生凋亡。然而，αvβ1整合素也是一种纤连蛋白受体，它与α5β1在相同的RGD基序上结合纤连蛋白，但并不能阻止相同细胞在纤连蛋白上发生凋亡。整合素α5亚基的胞质结构域是α5β1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与黏着斑激酶的酪氨酸磷酸化水平无关，黏着斑激酶是由整合素介导的细胞附着所诱导的。通过α5β1附着于纤连蛋白的细胞中，抗凋亡的Bcl-2蛋白表达升高；只有提供外源性Bcl-2时，通过αvβ1附着的细胞才能存活。因此，α5β1而非密切相关的αvβ1整合素似乎通过Bcl-2途径抑制凋亡性细胞死亡。
