title: The effect of G protein-coupled receptor kinase 2 (GRK2) on lactation and on proliferation of mammary epithelial cells from dairy cows.
abstract: Milk protein is an important component of milk and a nutritional source for human consumption. To better understand the molecular events underlying synthesis of milk proteins, the global gene expression patterns in mammary glands of dairy cow with high-quality milk (>3% milk protein; >3.5% milk fat) and low-quality milk (<3% milk protein; <3.5% milk fat) were examined via digital gene expression study. A total of 139 upregulated and 66 downregulated genes were detected in the mammary tissues of lactating cows with high-quality milk compared with the tissues of cows with low-quality milk. A pathway enrichment study of these genes revealed that the top 5 pathways that were differentially affected in the tissues of cows with high- versus low-quality milk involved metabolic pathways, cancer, cytokine-cytokine receptor interactions, regulation of the actin cytoskeleton, and insulin signaling. We also found that the G protein-coupled receptor kinase 2 (GRK2) was one of the most highly upregulated genes in lactating mammary tissue with low-quality milk compared with tissue with high-quality milk. The knockdown of GRK2 in cultured bovine mammary epithelial cells enhanced CSN2 expression and activated signaling molecules related to translation, including protein kinase B, mammalian target of rapamycin, and p70 ribosomal protein S6 kinase 1 (S6K1), whereas overexpression of GRK2 had the opposite effects. However, expression of genes involved in the mitogen-activated protein kinase pathway was positively regulated by GRK2. Therefore, GRK2 seems to act as a negative mediator of milk-protein synthesis via the protein kinase B-mammalian target of rapamycin signaling axis. Furthermore, GRK2 may negatively control milk-protein synthesis by activating the mitogen-activated protein kinase pathway in dairy cow mammary epithelial cells.
authors.affiliation: Key Lab of Dairy Science, Ministry of Education, Northeast Agricultural University, Harbin 150030, China.
authors.forename: Xiaoming
authors.initials: X
authors.lastname: Hou
authors.affiliation: Key Lab of Dairy Science, Ministry of Education, Northeast Agricultural University, Harbin 150030, China.
authors.forename: Hongliu
authors.initials: H
authors.lastname: Hu
authors.affiliation: Key Lab of Dairy Science, Ministry of Education, Northeast Agricultural University, Harbin 150030, China.
authors.forename: Ye
authors.initials: Y
authors.lastname: Lin
authors.affiliation: Key Lab of Dairy Science, Ministry of Education, Northeast Agricultural University, Harbin 150030, China.
authors.forename: Bo
authors.initials: B
authors.lastname: Qu
authors.affiliation: Key Lab of Dairy Science, Ministry of Education, Northeast Agricultural University, Harbin 150030, China.
authors.forename: Xuejun
authors.initials: X
authors.lastname: Gao
authors.affiliation: Key Lab of Dairy Science, Ministry of Education, Northeast Agricultural University, Harbin 150030, China. Electronic address: qzli@neau.edu.cn.
authors.forename: Qingzhang
authors.initials: Q
authors.lastname: Li
mesh_terms: D000818:Animals; D002417:Cattle; D004847:Epithelial Cells / Q000378:metabolism; D005260:Female; D006801:Humans; D007774:Lactation; D008321:Mammary Glands, Animal / Q000378:metabolism*; D008892:Milk / Q000378:metabolism; D008894:Milk Proteins / Q000378:metabolism
chemical_list: D008894:Milk Proteins
keywords: G protein-coupled receptor kinase 2; lactation; mammary gland; proliferation