Annexin A2 positively regulates milk synthesis and proliferation of bovine mammary epithelial cells through the mTOR signaling pathway

Annexin A2 (AnxA2) has been shown to play multiple roles in growth, development, and metabolism, but the functions of AnxA2 and the signaling pathways associated with AnxA2 are still not fully understood. In this study, we aim to reveal whether and how AnxA2 could be involved in milk synthesis and proliferation of bovine mammary epithelial cells (BMECs). Using gene function study approaches, we found that AnxA2 positively regulates PIP3 level, phosphorylation of mTOR, and protein levels of SREBP-1c and Cyclin D1 leading to milk synthesis and cell proliferation. We further observed that both AnxA2-36 kD phosphorylated form and AnxA2-33 kD protein could be induced from AnxA2-36 kD protein in BMECs under methionine, leucine, estrogen or prolactin stimulation. These above results strongly demonstrate that AnxA2 functions as a critical regulator for amino acid or hormone-induced milk synthesis and cell proliferation via the PI3K-mTOR-SREBP-1c/Cyclin D1 signaling pathway.