Secreted Kinase Phosphorylates Extracellular Proteins That Regulate Biomineralization

• Published in: Science (American Association for the Advancement of Science) 2012-06, Vol.336 (6085), p.1150-1153
• Main Authors: Tagliabracci, Vincent S., Engel, James L., Wen, Jianzhong, Wiley, Sandra E., Worby, Carolyn A., Kinch, Lisa N., Xiao, Junyu, Grishin, Nick V., Dixon, Jack E.
• Format: Article
• Language: English
• Subjects: Abnormalities, Multiple - genetics; Abnormalities, Multiple - metabolism; Amino Acid Motifs; Amino Acid Sequence; Animals; Biological and medical sciences; Biomineralization; Biomineralogy; Bones; Calcification, Physiologic; Casein; Casein Kinase I; Casein Kinases - metabolism; Caseins - metabolism; Cattle; Cell Line, Tumor; Cells; Cellular immunity; Cleft Palate - genetics; Cleft Palate - metabolism; Diseases of the osteoarticular system; Exophthalmos - genetics; Exophthalmos - metabolism; Extracellular Matrix Proteins - chemistry; Extracellular Matrix Proteins - genetics; Extracellular Matrix Proteins - metabolism; Genes; Glycoproteins - metabolism; Golgi Apparatus - enzymology; HEK293 Cells; HeLa Cells; Humans; Immunoblotting; Kinases; Malformations and congenital and or hereditary diseases involving bones. Joint deformations; Medical sciences; Microcephaly - genetics; Microcephaly - metabolism; Milk - enzymology; Mineralogy; Molecular Sequence Data; Mutation; Mutations; Osteopontin; Osteosclerosis - genetics; Osteosclerosis - metabolism; Pharmacology. Drug treatments; Phosphoproteins; Phosphorylation; Physiological regulation; Protein Sorting Signals; Proteins; Recombinant Fusion Proteins - chemistry; Recombinant Fusion Proteins - metabolism; Secretion; Secretory Pathway; Siblings; Substrate Specificity; T lymphocytes
• ISSN: 0036-8075; 1095-9203
• DOI: 10.1126/science.1217817

Protein phosphorylation is a fundamental mechanism regulating nearly every aspect of cellular life. Several secreted proteins are phosphorylated, but the kinases responsible are unknown. We identified a family of atypical protein kinases that localize within the Golgi apparatus and are secreted. 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, including the small integrin-binding ligand, N-linked glycoproteins (SIBLINGS). Consequently, mutations in Fam20C cause an osteosclerotic bone dysplasia in humans known as Raine syndrome. Fam20C is thus a protein kinase dedicated to the phosphorylation of extracellular proteins.