title: Secreted kinase phosphorylates extracellular proteins that regulate biomineralization.
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.
authors.affiliation: Department of Pharmacology, University of California, San Diego, La Jolla, CA 92093-0721, USA.
authors.forename: Vincent S
authors.initials: VS
authors.lastname: Tagliabracci
authors.forename: James L
authors.initials: JL
authors.lastname: Engel
authors.forename: Jianzhong
authors.initials: J
authors.lastname: Wen
authors.forename: Sandra E
authors.initials: SE
authors.lastname: Wiley
authors.forename: Carolyn A
authors.initials: CA
authors.lastname: Worby
authors.forename: Lisa N
authors.initials: LN
authors.lastname: Kinch
authors.forename: Junyu
authors.initials: J
authors.lastname: Xiao
authors.forename: Nick V
authors.initials: NV
authors.lastname: Grishin
authors.forename: Jack E
authors.initials: JE
authors.lastname: Dixon
mesh_terms: D000015:Abnormalities, Multiple / Q000235:genetics / Q000378:metabolism; D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D000818:Animals; D002113:Calcification, Physiologic; D047389:Casein Kinase I; D047388:Casein Kinases / Q000378:metabolism; D002364:Caseins / Q000378:metabolism*; D002417:Cattle; D045744:Cell Line, Tumor; D002972:Cleft Palate / Q000235:genetics / Q000378:metabolism; D005094:Exophthalmos / Q000235:genetics / Q000378:metabolism; D016326:Extracellular Matrix Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D006023:Glycoproteins / Q000378:metabolism; D006056:Golgi Apparatus / Q000201:enzymology*; D057809:HEK293 Cells; D006367:HeLa Cells; D006801:Humans; D008831:Microcephaly / Q000235:genetics / Q000378:metabolism; D008892:Milk / Q000201:enzymology; D008969:Molecular Sequence Data; D009154:Mutation; D053495:Osteopontin; D010026:Osteosclerosis / Q000235:genetics / Q000378:metabolism; D010766:Phosphorylation; D021382:Protein Sorting Signals; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000378:metabolism; D055571:Secretory Pathway; D013379:Substrate Specificity
chemical_list: D002364:Caseins; D016326:Extracellular Matrix Proteins; D006023:Glycoproteins; D021382:Protein Sorting Signals; D011993:Recombinant Fusion Proteins; D053495:Osteopontin; D047389:Casein Kinase I; D047388:Casein Kinases; C524449:FAM20C protein, human