The Tagliabracci lab studies the phosphorylation of extracellular proteins by a novel family of secreted kinases. This kinase family is so different from canonical kinases that it was not included as a branch on the human kinome tree.
One member, family with sequence similarity 20, member C (Fam20C), is the bona fide Golgi casein kinase, an enzyme that escaped identification for many years. Fam20C contains a signal peptide that directs it to the lumen of the secretory pathway where it phosphorylates proteins destined for secretion on S-x-E/pS motifs.
The importance of this discovery is underscored by the fact that about 75 percent of human serum, plasma, and cerebrospinal fluid phosphoproteins are phosphorylated within this motif. Indeed, Fam20C phosphorylates hundreds of secreted proteins and it appears to be responsible for generating the majority of the secreted phosphoproteome.
Functional annotations of Fam20C substrates suggest roles for the kinase in a broad spectrum of physiological processes, including lipid metabolism, wound healing, cell migration, biomineralization, inflammation, nervous system development, and many others.
Understanding the functional implications of these phosphorylation events and how these modifications impact human biology are major objectives of the laboratory.