Milk proteins are crucial for the development of all newborn mammals and caseins constitute the major proteins in mammalian milk. b- and k-caseins are the only caseins present in human milk. The b-casein/k-casein ratio is higher in colostrum than in transitional and mature milk and is related to a better digestibility of colostrum casein micelles by the neonate during the first days of life. Human b-casein-encoding gene (Bca) contains a highly phosphorylated site, which is responsible for the calcium-binding capacity of b-casein. A common set of transcription factors are required for the expression of b-casein. Multiple binding sites for Stat5, C/EBPb (CCAAT/enchancer-binding protein) and several half-sites for glucocorticoid receptor (GR) are identified in the distal human enhancer of the b-casein gene. b-casein gene transcription is regulated primarily by a composite response element (CoRE), which integrates signaling from the lactogenic hormones PRL, insulin and hydrocortisone in mammary epithelial cells. NFkB functions as a negative regulator of b-casein gene expression during pregnancy by interfering with Stat5 tyrosine phosphorylation
