Journal
SCIENCE
Volume 336, Issue 6085, Pages 1150-1153Publisher
AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/science.1217817
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Funding
- NIH [DK018849-36, DK018024-37, GM094575]
- NIH/National Cancer Institute [T32 CA009523]
- Welch Foundation [I-1505]
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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.
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