A cell signal pathway involving laminin-5, α3β1 integrin, and mitogen-activated protein kinase can regulate epithelial cell proliferation
A cell signal pathway involving laminin-5, α3β1 integrin, and mitogen-activated protein kinase can regulate epithelial cell proliferation
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DOI：
10.1091/mbc.10.2.259
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发表时间：
1999-02-01
影响因子：
3.3
通讯作者：
Jones, JCR
中科院分区：
文献类型：
--
作者：
Gonzales, M;Haan, K;Jones, JCR
层粘连蛋白-5（LN 5）是上皮组织基底膜的基质成分，在上皮细胞锚定到下层结缔组织的启动和维持中起重要作用。在这里，我们表明，两个不同的LN 5功能抑制抗体，这两个结合的α 3亚基的球状域，抑制上皮细胞的增殖。这些相同的抗体也诱导丝裂原活化蛋白激酶活性的降低。功能干扰性LN 5抗体对增殖的抑制在去除抗体后被逆转，并且可以通过向抗体处理的细胞提供外源性LN 5和大鼠尾胶原蛋白来克服。由于上皮细胞使用整合素受体α 3 β 1与LN 5和大鼠尾胶原蛋白相互作用，我们接下来研究了整合素α 3 β 1参与介导LN 5增殖影响的可能性。干扰功能的α 3整联蛋白抗体显著抑制人上皮细胞的增殖。此外，β 1整联蛋白的抗体活化恢复了用LN 5功能干扰抗体处理的上皮细胞的增殖。这些数据表明，包含LN 5和α 3 β 1整联蛋白的复合物是多功能的，不仅有助于上皮细胞粘附，而且有助于通过涉及促分裂原活化蛋白激酶的信号传导途径调节细胞生长。我们讨论了我们的研究，根据最近的证据表明，LN 5的表达上调在肿瘤的前端，在那里它可能在肿瘤细胞增殖中发挥作用。
Laminin-5 (LN5) is a matrix component of epithelial tissue basement membranes and plays an important role in the initiation and maintenance of epithelial cell anchorage to the underlying connective tissue. Here we show that two distinct LN5 function-inhibitory antibodies, both of which bind the globular domain of the alpha 3 subunit, inhibit proliferation of epithelial cells. These same antibodies also induce a decrease in mitogen-activated protein kinase activity. Inhibition of proliferation by the function-perturbing LN5 antibodies is reversed upon removal of the antibodies and can be overcome by providing the antibody-treated cells with exogenous LN5 and rat tail collagen. Because epithelial cells use the integrin receptor alpha 3 beta 1 to interact with both LN5 and rat tail collagen, we next investigated the possibility that integrin alpha 3 beta 1 is involved in mediating the proliferative impact of LN5. Proliferation of human epithelial cells is significantly inhibited by a function-perturbing alpha 3 integrin antibody. In addition, antibody activation of beta 1 integrin restores the proliferation of epithelial cells treated with LN5 function-perturbing antibodies. These data indicate that a complex comprising LN5 and alpha 3 beta 1 integrin is multifunctional and contributes not only to epithelial cell adhesion but also to the regulation of cell growth via a signaling pathway involving mitogen-activated protein kinase. We discuss our study in light of recent evidence that LN5 expression is up-regulated at the leading tips of tumors, where it may play a role in tumor cell proliferation.