Sulfation of von Willebrand factor

Journal Article · Sat Dec 15 00:00:00 EST 1990 · Blood (Journal of Hematology); (USA)

OSTI ID:6249142

Carew, J A; Browning, P J; Lynch, D C ^[1]

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1. Harvard Medical School, Boston, MA (USA)

von Willebrand factor (vWF) is a multimeric adhesive glycoprotein essential for normal hemostasis. We have discovered that cultured human umbilical vein endothelial cells incorporate inorganic sulfate into vWF. Following immunoisolation and analysis by polyacrylamide or agarose gel electrophoresis, metabolically labeled vWF was found to have incorporated (35S)-sulfate into all secreted multimer species. The time course of incorporation shows that sulfation occurs late in the biosynthesis of vWF, near the point at which multimerization occurs. Quantitative analysis suggests the presence, on average, of one molecule of sulfate per mature vWF subunit. Virtually all the detectable sulfate is released from the mature vWF subunit by treatment with endoglycosidases that remove asparagine-linked carbohydrates. Sulfated carbohydrate was localized first to the N-terminal half of the mature subunit (amino acids 1 through 1,365) by partial proteolytic digestion with protease V8; and subsequently to a smaller fragment within this region (amino acids 273 through 511) by sequential digestions with protease V8 and trypsin. Thus, the carbohydrate at asparagine 384 and/or 468 appears to be the site of sulfate modification. Sodium chlorate, an inhibitor of adenosine triphosphate-sulfurylase, blocks sulfation of vWF without affecting either the ability of vWF to assemble into high molecular weight multimers or the ability of vWF multimers to enter Weible-Palade bodies. The stability of vWF multimers in the presence of an endothelial cell monolayer also was unaffected by the sulfation state. Additionally, we have found that the cleaved propeptide of vWF is sulfated on asparagine-linked carbohydrate.

• OSTI ID: 6249142
• Journal Information: Blood (Journal of Hematology); (USA), Vol. 76:12; ISSN 0006-4971
• Country of Publication: United States
• Language: English

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59 BASIC BIOLOGICAL SCIENCES
GLYCOPROTEINS
METABOLISM
ELECTROPHORESIS
ENDOTHELIUM
ENZYME INHIBITORS
MAN
MOLECULAR WEIGHT
QUANTITATIVE CHEMICAL ANALYSIS
SERINE PROTEINASES
SULFATES
SULFUR 35
TRACER TECHNIQUES
ANIMAL TISSUES
ANIMALS
BETA DECAY RADIOISOTOPES
BETA-MINUS DECAY RADIOISOTOPES
BODY
CHEMICAL ANALYSIS
DAYS LIVING RADIOISOTOPES
ENZYMES
EVEN-ODD NUCLEI
HYDROLASES
ISOTOPE APPLICATIONS
ISOTOPES
LIGHT NUCLEI
MAMMALS
NUCLEI
ORGANIC COMPOUNDS
OXYGEN COMPOUNDS
PEPTIDE HYDROLASES
PRIMATES
PROTEINS
RADIOISOTOPES
SULFUR COMPOUNDS
SULFUR ISOTOPES
TISSUES
VERTEBRATES
550501* - Metabolism- Tracer Techniques