Abstract

Tudor staphylococcal nuclease (Tudor‐SN) participates in milk synthesis and cell proliferation in response to prolactin (PRL) and plays a regulatory role on mTOR phosphorylation. However, the complicated molecular mechanism of Tudor‐SN regulating milk protein synthesis and cell proliferation still remains to be illustrated. In present study, we observed that the proteins level of phosphorylated Tudor‐SN and phosphorylated STAT5 were simultaneously enhanced upon PRL treatment in bovine mammary epithelial cells (BMECs). Tudor‐SN overexpression and knockdown experiment showed that Tudor‐SN positively regulated the synthesis of milk protein, cell proliferation and the phosphorylation of STAT5, which was dependent on Tudor‐SN phosphorylation. STAT5 knockdown experiment showed that Tudor‐SN stimulated mTOR pathway through regulating STAT5 activation, which was required for PRL to activate the mTOR pathway. Thus, these results demonstrate the primary mechanism of Tudor‐SN coordinating with STAT5 to regulate milk protein synthesis and cell proliferation under stimulation of PRL in BMECs, which may provide some new perspectives for increasing milk production.

摘要

Tudor 葡萄球菌核酸酶 (Tudor-SN) 参与乳汁合成和细胞增殖以响应催乳素 (PRL)，并对 mTOR 磷酸化起调节作用。然而，Tudor-SN 调节​​乳蛋白合成和细胞增殖的复杂分子机制仍有待阐明。在本研究中，我们观察到牛乳腺上皮细胞 (BMEC) 中磷酸化 Tudor-SN 和磷酸化 STAT5 的蛋白质水平在 PRL 处理后同时增强。Tudor-SN 过表达和敲低实验表明，Tudor-SN 正向调节乳蛋白的合成、细胞增殖和 STAT5 的磷酸化，这依赖于 Tudor-SN 磷酸化。STAT5 敲低实验表明，Tudor-SN 通过调节 STAT5 激活来刺激 mTOR 通路，这是 PRL 激活 mTOR 通路所必需的。因此，这些结果证明了 Tudor-SN 与 STAT5 协同调节 BMECs 中 PRL 刺激下乳蛋白合成和细胞增殖的主要机制，这可能为增加牛奶产量提供一些新的视角。