title: A secretory kinase complex regulates extracellular protein phosphorylation.
abstract: Although numerous extracellular phosphoproteins have been identified, the protein kinases within the secretory pathway have only recently been discovered, and their regulation is virtually unexplored. Fam20C is the physiological Golgi casein kinase, which phosphorylates many secreted proteins and is critical for proper biomineralization. Fam20A, a Fam20C paralog, is essential for enamel formation, but the biochemical function of Fam20A is unknown. Here we show that Fam20A potentiates Fam20C kinase activity and promotes the phosphorylation of enamel matrix proteins in vitro and in cells. Mechanistically, Fam20A is a pseudokinase that forms a functional complex with Fam20C, and this complex enhances extracellular protein phosphorylation within the secretory pathway. Our findings shed light on the molecular mechanism by which Fam20C and Fam20A collaborate to control enamel formation, and provide the first insight into the regulation of secretory pathway phosphorylation.
authors: Department of Pharmacology, University of California, San Diego, La Jolla, United States.
authors: Jixin
authors: J
authors: Cui
authors: Department of Pharmacology, University of California, San Diego, La Jolla, United States.
authors: Junyu
authors: J
authors: Xiao
authors: Department of Pharmacology, University of California, San Diego, La Jolla, United States.
authors: Vincent S
authors: VS
authors: Tagliabracci
authors: Department of Pharmacology, University of California, San Diego, La Jolla, United States.
authors: Jianzhong
authors: J
authors: Wen
authors: Department of Pharmacology, University of California, San Diego, La Jolla, United States.
authors: Meghdad
authors: M
authors: Rahdar
authors: Department of Pharmacology, University of California, San Diego, La Jolla, United States.
authors: Jack E
authors: JE
authors: Dixon
mesh_terms: D000565:Ameloblasts / Q000166:cytology / Q000378:metabolism*; D000595:Amino Acid Sequence; D000818:Animals; D047389:Casein Kinase I / Q000235:genetics* / Q000378:metabolism; D002460:Cell Line; D003746:Dental Enamel Proteins / Q000235:genetics* / Q000378:metabolism; D016326:Extracellular Matrix Proteins / Q000235:genetics* / Q000378:metabolism; D005260:Female; D018703:Founder Effect; D015870:Gene Expression; D005786:Gene Expression Regulation; D006801:Humans; D007915:Lepidoptera; D008321:Mammary Glands, Animal / Q000166:cytology / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D010766:Phosphorylation; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D015398:Signal Transduction
chemical_list: D003746:Dental Enamel Proteins; D016326:Extracellular Matrix Proteins; C571509:FAM20A protein, human; D011994:Recombinant Proteins; C109069:enamel matrix proteins; D047389:Casein Kinase I; C524449:FAM20C protein, human
keywords: biochemistry; extracellular protein phosphorylation; human; kinase complex; mouse; pseudokinase; secretory pathway phosphorylation; tooth enamel formation