Milk may contain the calcium that helps build strong bones, but we rely on subtle biological interactions to absorb and make use of the mineral. In one of these interactions, called phosphorylation, a kinase enzyme affixes phosphates to proteins. With correct phosphorylation, proteins are able to bind calcium to form bones and teeth.
For over a century, scientists have known that the milk protein casein contains phosphate. In a study published June 1, 2012, in Science, researchers led by Jack E. Dixon, HHMI vice president and chief scientific officer, found that Fam20C—a member of the seldom-studied Fam20 family of proteins—is responsible for the phosphorylation of casein.
Scouring old scientific reports, the researchers also discovered something unexpected: mutations in Fam20C had been reported in patients with Raine syndrome—a fatal disease in which bones become too dense. Dixon’s team developed a cell line with the Raine syndrome mutations. “Every single one of these mutations inactivated the Fam20C kinase and prevented it from being secreted,” says Dixon. The mutations affected phosphorylation of casein as well as several other proteins involved in enamel and bone formation.
“What we’ve discovered isn’t just the casein kinase,” Dixon says. “It’s a whole new branch on the kinase tree that seems to play an important role in bone and teeth formation.”