α5β1 integrin protects intestinal epithelial cells from apoptosis through a phosphatidylinositol 3-kinase and protein kinase B-dependent pathway
α5β1 integrin protects intestinal epithelial cells from apoptosis through a phosphatidylinositol 3-kinase and protein kinase B-dependent pathway
复制标题
DOI：
10.1091/mbc.11.6.1973
复制
发表时间：
2000-06-01
影响因子：
3.3
通讯作者：
Juliano, RL
中科院分区：
文献类型：
--
作者：
Lee, JW;Juliano, RL
胃肠上皮的更新涉及终末分化和程序性细胞死亡的协调过程。整联蛋白参与了多种细胞类型中凋亡过程的控制。在这里，我们研究整合素在调节胃肠道上皮细胞凋亡的作用与使用大鼠小肠上皮细胞系（RIE 1）作为模型。整合素α 5亚基在RIE 1细胞中的过表达赋予了对几种促凋亡刺激的保护作用。相反，整合素α 2亚基的过度表达对细胞存活没有影响。α 5亚基的抗ayoptotic效果部分保留了一个突变的版本，有一个截断的胞质结构域。用磷脂酰肌醇3-激酶（PI-3-kinase）抑制剂处理后，全长或截短的α 5亚基的抗凋亡作用被逆转，表明α 5 β 1整联蛋白可能与PI-3-kinase/Akt存活途径相互作用。当过表达α 5的细胞被允许粘附到纤连蛋白上时，蛋白激酶B（PKB）/Akt有中度激活，而在粘附到胶原蛋白上的α 2过表达细胞中没有观察到这种作用。此外，在过表达α 5和粘附纤连蛋白的细胞中，生长因子刺激PKB/Akt的能力显著增强;同样，这在过表达α 2亚基和粘附胶原蛋白或纤连蛋白的细胞中未观察到。在RIE细胞中显性阴性形式的PKB/Akt的表达被阻断以增强α 5的细胞存活能力。因此，α 5 β 1整联蛋白似乎通过选择性增强PI-3-激酶Akt存活途径的活性来保护肠上皮细胞免受促凋亡刺激。
Renewal of the gastrointestinal epithelium involves a coordinated process of terminal differentiation and programmed cell death. Integrins have been implicated in the control of apoptotic processes in various cell types. Here we examine the role of integrins in the regulation of apoptosis in gastrointestinal epithelial cells with the use of a rat small intestinal epithelial cell line (RIE1) as a model. Overexpression of the integrin alpha 5 subunit in RIE1 cells conferred protection against several proapoptotic stimuli. In contrast, overexpression of the integrin alpha 2 subunit had no effect on cell survival. The antiayoptotic effect of the alpha 5 subunit was partially retained by a mutated version that had a truncation of the cytoplasmic domain. The antiapoptotic effects of the full-length or truncated a5 subunit were reversed upon treatment with inhibitors of phosphatidylinositol 3-kinase (PI-3-kinase), suggesting that the alpha 5 beta 1 integrin might interact with the PI-3-kinase/Akt survival pathway. When cells overexpressing alpha 5 were allowed to adhere to fibronectin, there was a moderate activation of protein kinase B (PKB)/Akt, whereas no such effect was seen in alpha 2-overexpressing cells adhering to collagen. Furthermore, in cells overexpressing alpha 5 and adhering to fibronectin, there was a dramatic enhancement of the ability of growth factors to stimulate PKB/Akt; again, this was not seen in cells overexpressing alpha 2 subunit and adhering to collagen or fibronectin. Expression of a dominant negative version of PKB/Akt in RIE cells blocked to ability of alpha 5 to enhance cell survival. Thus, the alpha 5 beta 1 integrin seems to protect intestinal epithelial cells against proapoptotic stimuli by selectively enhancing the activity of the PI-3-kinnaseAkt survival pathway.