Sialyltransferase ST3Gal-IV operates as a dominant modifier of hemostasis by concealing asialoglycoprotein receptor ligands. Proceedings of the National Academy of Sciences of the United States of America. [Proc Natl Acad Sci U S A] Journal article

Title	Sialyltransferase ST3Gal-IV operates as a dominant modifier of hemostasis by concealing asialoglycoprotein receptor ligands.
Author(s)	Ellies LG, Ditto D, Levy GG, Wahrenbrock M, Ginsburg D, Varki A, Le DT, Marth JD
Institution	Howard Hughes Medical Institute and Department of Cellular and Molecular Medicine, 9500 Gilman Drive 0625, University of California San Diego, La Jolla, CA 92093, USA.
Source	Proc Natl Acad Sci U S A 2002 Jul 23; 99(15):10042-7.
MeSH	Animals Asialoglycoprotein Receptor DNA Primers Factor VIII Half-Life Hemostasis Lectins Ligands Metabolic Clearance Rate Mice Mutagenesis, Site-Directed Polymerase Chain Reaction Receptors, Cell Surface Recombinant Proteins Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S. Sialyltransferases Thrombocytopenia Transcription, Genetic von Willebrand Factor
Abstract	A number of poorly characterized genetic modifiers contribute to the extensive variability of von Willebrand disease, the most prevalent bleeding disorder in humans. We find that a genetic lesion inactivating the murine ST3Gal-IV sialyltransferase causes a bleeding disorder associated with an autosomal dominant reduction in plasma von Willebrand factor (VWF) and an autosomal recessive thrombocytopenia. Although both ST3Gal-IV and ST6Gal-I sialyltransferases mask galactose linkages implicated as asialoglycoprotein receptor ligands, only ST3Gal-IV deficiency promotes asialoglycoprotein clearance mechanisms with a reduction in plasma levels of VWF and platelets. Exposed galactose on VWF was also found in a subpopulation of humans with abnormally low VWF levels. Oligosaccharide branch-specific sialylation by the ST3Gal-IV sialyltransferase is required to sustain the physiologic half-life of murine hemostatic components and may be an important modifier of plasma VWF level in humans.
Language	eng
Pub Type(s)	Journal Article
PubMed ID	12097641

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