Novel Secreted Protein Kinases

Abstract

Protein phosphorylation is a fundamental mechanism regulating nearly every aspect of cellular life. Several secreted proteins are phosphorylated but the kinases responsible for these phosphorylations are unknown. We identified a family of atypical protein kinases that localize within the Golgi apparatus and are secreted. A member of this protein kinase family, Fam20C, appears to be the Golgi casein kinase that phosphorylates secretory pathway proteins within S‐x‐E motifs. Fam20C phosphorylates the caseins and several secreted proteins implicated in biomineralization. Mutations in Fam20C cause an osteoscierotic bone dysplasia in humans known as Raine syndrome. Fam20C phosphorylates dozens of other substrates as well, and is thus a protein kinase dedicated to the phosphorylation of extracellular proteins.