BETA-LACTOGLOBULIN AND ALPHA-LACTALBUMIN AS POTENTIAL MODULATORS OF MAMMARY CELLULAR-ACTIVITY - A CA2+-RESPONSIVE MODEL SYSTEM USING ACID PHOSPHOPROTEIN PHOSPHATASES

It has been observed that beta-lactoglobulin of cow's milk inhibits the hydrolysis of p-nitrophenyl phosphate by phosphoprotein phosphatases from bovine spleen and lactating mammary gland. Kinetic studies indicate that the inhibition of p-nitrophenyl phosphate hydrolysis involves binding to the enzyme by beta-lactoglobulin. Alkaline denaturation of the beta-lactoglobulin molecule decreases the inhibition. This inhibition is reversed by Ca2+-binding to sites on beta-lactoglobulin with K(D) equal to 3 mM, or by salt concentration > 100 mM. alpha-Lactalbumin functions in a similar fashion with both the mammary and spleen enzymes. Since both these whey proteins and the milk phosphatase are secreted by Golgi, this in vitro reaction may serve as a model system for enzyme regulation in mammary secretory vessicles where the [Ca2+]free concentration approaches 5 to 8mM. Formation of enzyme-protein complexes in Golgi could in turn be effected by the binding of a ligand such as Ca2+ to "weak" sites. Thus protein-protein interactions which limit the activity of an enzyme may in turn be modulated by Ca2+ binding to the protein.