Integrin α5/β1 mediates fibronectin-dependent epithelial cell proliferation through epidermal growth factor receptor activation
Integrin α5/β1 mediates fibronectin-dependent epithelial cell proliferation through epidermal growth factor receptor activation
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DOI：
10.1091/mbc.11.7.2485
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发表时间：
2000-07-01
影响因子：
3.3
通讯作者：
Li, XF
中科院分区：
文献类型：
--
作者：
Kuwada, SK;Li, XF
将人整合素α5转染至整合素α5/β1阴性肠上皮细胞系Caco-2中，以研究EGF受体（EGFR）和整合素α5/β1信号相互作用参与上皮细胞增殖。在未包被或纤连蛋白包被的塑料上，整合素α5和对照（仅载体）转染子以相似的速率生长。在存在 EGFR 拮抗 mAb 225 的情况下，整合素 α5 转染子和对照在塑料上的生长受到显着抑制。然而，当在纤连蛋白上培养时，整联蛋白α5转染子的生长不受mAb 225的抑制。mAb 225介导的对整联蛋白α5转染子的纤连蛋白生长抑制的逆转与EGFR的激活、MAPK的激活和增殖细胞核抗原的表达相关。 EGFR 激酶活性对于 MAPK 激活和整合素 α 5/β 1 介导的细胞增殖都是必需的。尽管当整合素α5转染细胞或对照细胞在纤连蛋白上培养时会发生EGFR激活，但EGFR与SHC的共沉淀仅在整合素α5转染细胞中得以证实。这些结果表明整合素α5/β1通过激活EGFR介导纤连蛋白诱导的上皮细胞增殖。
Human integrin alpha 5 was transfected into the integrin alpha 5/beta 1-negative intestinal epithelial cell line Caco-2 to study EGF receptor (EGFR) and integrin alpha 5/beta 1 signaling interactions involved in epithelial cell proliferation. On uncoated or fibronectin-coated plastic, the integrin alpha 5 and control (vector only) transfectants grew at similar rates. In the presence of the EGFR antagonistic mAb 225, the integrin alpha 5 transfectants and controls were significantly growth inhibited on plastic. However, when cultured on fibronectin, the integrin alpha 5 transfectants were not growth inhibited by mAb 225. The reversal of mAb 225-mediated growth inhibition on fibronectin for the integrin alpha 5 transfectants correlated with activation of the EGFR, activation of MAPK, and expression of proliferating cell nuclear antigen. EGFR kinase activity was necessary for both MAPK activation and integrin alpha 5/beta 1-mediated cell proliferation. Although EGFR activation occurred when either the integrin alpha 5-transfected or control cells were cultured on fibronectin, coprecipitation of the EGFR with SHC could be demonstrated only in the integrin alpha 5-transfected cells. These results suggest that integrin alpha 5/beta 1 mediates fibronectin-induced epithelial cell proliferation through activation of the EGFR.