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Science 336 (6085): 1150-1153

Copyright © 2012 by the American Association for the Advancement of Science

Secreted Kinase Phosphorylates Extracellular Proteins That Regulate Biomineralization

Vincent S. Tagliabracci,1 James L. Engel,1 Jianzhong Wen,1 Sandra E. Wiley,1 Carolyn A. Worby,1 Lisa N. Kinch,2 Junyu Xiao,1 Nick V. Grishin,2,3 Jack E. Dixon1,3,*

Abstract: 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.

1 Department of Pharmacology, University of California, San Diego, La Jolla, CA 92093–0721, USA.
2 University of Texas, Southwestern Medical Center, Dallas, TX 75390–9050, USA.
3 Howard Hughes Medical Institute, Chevy Chase, MD 20815–6789, USA.

* To whom correspondence should be addressed. E-mail: jedixon{at}

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