Myotonic dystrophy-related CDC42-binding kinase alpha (MRCKa) mediates methionine-and leucine-stimulated β-casein synthesis in bovine mammary epithelial cells via targeting mTOR

文献类型： 外文期刊

第一作者： Wang, Fang

作者： Wang, Fang;Ma, Lu;Bu, Dengpan;Wang, Fang;Dijkstra, Jan;Gao, Xuejun;Bu, Dengpan;Bu, Dengpan

作者机构：

关键词： Protein kinase B; Amino acid; Myotonic dystrophy-related CDC42-binding; kinase alpha; Mammary gland; Milk synthesis; Phosphatidylinositol 3-kinase

期刊名称：ANIMAL NUTRITION （ 影响因子：7.5； 五年影响因子：7.3 ）

ISSN： 2405-6383

年卷期： 2025 年 21 卷

页码：

收录情况： SCI

摘要： Amino acids (AA), including methionine (Met) and leucine (Leu), stimulate milk synthesis in bovine mammary epithelial cells (BMEC) via activation of protein kinase mechanistic target of rapamycin (mTOR). In this study, we further explored the potential role of myotonic dystrophy-related CDC42-binding kinase alpha (MRCKa), previously identified as a critical mediator of prolactin-stimulated milk synthesis in BMEC. Administering different doses (0, 0.2, 0.4, 0.6, 0.8 mM) of Met or Leu to a primary BMEC culture showed that 0.6 mM was the optimal dose for stimulating beta-casein production with both AA. At this dose, Met and Leu independently evoked higher (P < 0.05) protein levels of beta-casein, MRCKa and sterol regulatory element-binding protein 1 (SREBP1), and increased (P < 0.05) phosphorylation of mTOR (Ser2448) and phosphatidylinositol 3-kinase (PI3K) (Tyr317) after 24 h. The stimulatory effects of both AA on relative protein level of beta-casein, phosphorylation of mTOR, and phosphorylation of protein kinase B (PKB) (Thr308), were blocked by silencing MRCKa expression (P < 0.05). Whereas, that on the phosphorylation of PI3K remained intact (P 1/4 0.385). Inhibiting PI3K with LY2940 02 blocked Met-and Leu-induced protein expression of MRCKa and beta-casein and phosphorylation of mTOR (P < 0.05). Overexpression of MRCKa increased protein levels of (3-casein and phosphorylation of mTOR, which was prevented by PKB inhibitor MK2206 (P < 0.05). Our results indicate that MRCKa is a key mediator of the Met-and Leu-induced signaling cascade, acting downstream of PI3K and upstream of PKB to regulate beta-casein synthesis in BMEC. (c) 2025 The Authors. Publishing services by Elsevier B.V. on behalf of KeAi Communications Co. Ltd. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

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