ArticleProceedings of the National Academy of Sciences of the United States of America2014
Xylose phosphorylation functions as a molecular switch to regulate proteoglycan biosynthesis.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 69 papers.
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Who cites it
69 citing papers in PubMed, 108 citations in OpenAlex.
- Discovery of a Functional Sequon for Chondroitin Sulfate Glycosylation.Research square · 2026Article
- Xylosyltransferase engineering to manipulate proteoglycans in mammalian cells.Nature chemical biology · 2026Article
- FUT1- and GAL3ST2-mediated cellular glycan remodeling broadly restricts sialic acid-dependent viral infections.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Xylose phosphatase activity of dystroglycan self-regulates its receptor function.bioRxiv : the preprint server for biology · 2025Article
- Congenital disorders caused by aberrations in the biosynthesis of chondroitin/dermatan sulfate.Journal of human genetics · 2025Review
- B3GALT6 mutations lead to compromised connective tissue biomechanics in Ehlers-Danlos syndrome.JCI insight · 2025Article
- Recent Advances in Enzymes and Chemoenzymatic Synthesis of Tetrasaccharide Linkage Region of Proteoglycans.Chembiochem : a European journal of chemical biology · 2025Review
- Article
- FAM20B-Catalyzed Glycosylation Regulates the Chondrogenic and Osteogenic Differentiation of the Embryonic Condyle by Controlling IHH Diffusion and Release.International journal of molecular sciences · 2025Article
- Genetic variability in proteoglycan biosynthetic genes reveals new facets of heparan sulfate diversity.Essays in biochemistry · 2024Review
- Solid-Phase-Supported Chemoenzymatic Synthesis and Analysis of Chondroitin Sulfate Proteoglycan Glycopeptides.Angewandte Chemie (International ed. in English) · 2024Article
- Protein glycosylation in cardiovascular health and disease.Nature reviews. Cardiology · 2024Review
- Chemo-enzymatic synthesis of tetrasaccharide linker peptides to study the divergent step in glycosaminoglycan biosynthesis.Glycobiology · 2024Article
- A periodic table of monosaccharides.Glycobiology · 2024Article
- FAM20A is a golgi-localized Type II transmembrane protein.Scientific reports · 2024Article
- Proteoglycan inhibition of canonical BMP-dependent cartilage maturation delays endochondral ossification.Development (Cambridge, England) · 2024Article
- Role of proteoglycan synthesis genes in osteosarcoma stem cells.Frontiers in oncology · 2024Article
- Molecular mechanism of decision-making in glycosaminoglycan biosynthesis.Nature communications · 2023Article
- Deficiency ofInternational journal of molecular sciences · 2023Article
- Potential Role of Protein Kinase FAM20C on the Brain in Raine Syndrome, an In Silico Analysis.International journal of molecular sciences · 2023Article
9 more citing papers are in PubMed but not listed here.
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8 authors at 2 institutions in 1 country.
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Abstract
Most eukaryotic cells elaborate several proteoglycans critical for transmitting biochemical signals into and between cells. However, the regulation of proteoglycan biosynthesis is not completely understood. We show that the atypical secretory kinase family with sequence similarity 20, member B (Fam20B) phosphorylates the initiating xylose residue in the proteoglycan tetrasaccharide linkage region, and that this event functions as a molecular switch to regulate subsequent glycosaminoglycan assembly. Proteoglycans from FAM20B knockout cells contain a truncated tetrasaccharide linkage region consisting of a disaccharide capped with sialic acid (Siaα2-3Galβ1-4Xylβ1) that cannot be further elongated. We also show that the activity of galactosyl transferase II (GalT-II, B3GalT6), a key enzyme in the biosynthesis of the tetrasaccharide linkage region, is dramatically increased by Fam20B-dependent xylose phosphorylation. Inactivating mutations in the GALT-II gene (B3GALT6) associated with Ehlers-Danlos syndrome cause proteoglycan maturation defects similar to FAM20B deletion. Collectively, our findings suggest that GalT-II function is impaired by loss of Fam20B-dependent xylose phosphorylation and reveal a previously unappreciated mechanism for regulation of proteoglycan biosynthesis.
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