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Dependence on Vitam...
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Carlsson, SofiaLund University, Sweden;Skåne University Hospital, Sweden
(author)
Dependence on Vitamin K-dependent Protein S for Eukaryotic Cell Secretion of the β-Chain of C4b-binding Protein
- Article/chapterEnglish2010
Publisher, publication year, extent ...
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The American Society for Biochemistry and Molecular Biology,2010
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Numbers
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LIBRIS-ID:oai:DiVA.org:lnu-111089
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https://urn.kb.se/resolve?urn=urn:nbn:se:lnu:diva-111089URI
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https://doi.org/10.1074/jbc.m110.148452DOI
Supplementary language notes
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Language:English
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Summary in:English
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Subject category:ref swepub-contenttype
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Subject category:art swepub-publicationtype
Notes
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The anticoagulant vitamin K-dependent protein S (PS) circulates in plasma in two forms, 30% free and 70% being bound to the complement regulatory protein C4b-binding protein (C4BP). The major C4BP isoform consists of 7 α-chains and 1 β-chain (C4BPβ+), the chains being linked by disulfide bridges. PS binds to the β-chain with high affinity. In plasma, PS is in molar excess over C4BPβ+ and due to the high affinity, all C4BPβ+ molecules contain a bound PS. Taken together with the observation that PS-deficient patients have decreased levels of C4BPβ+, this raises the question of whether PS is important for secretion of the β-chain from the cell. To test this hypothesis, HEK293 cells were stably and transiently transfected with β-chain cDNA in combinations with cDNAs for PS and/or the α-chain. The concentration of β-chains in the medium increased after co-transfection with PS cDNA, but not by α-chain cDNA, suggesting secretion of the β-chains from the cells to be dependent on concomitant synthesis of PS, but not of the α-chains. Thus, β-chains that were not disulfide-linked to the α-chains were secreted in complex with PS, either as monomers or dimers. Pulse-chase demonstrated that the complexes between PS and β-chain were formed intracellularly, in the endoplasmic reticulum. In conclusion, our results demonstrate that successful secretion of β-chains depends on intracellular complex formation with PS, but not on the α-chains. This provides an explanation for the decreased β-chain levels observed in PS-deficient patients.
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Dahlbäck, BjörnLund University, Sweden;Skåne University Hospital, Sweden
(author)
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Lund University, Sweden;Skåne University Hospital, Sweden
(creator_code:org_t)
Related titles
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In:Journal of Biological Chemistry: The American Society for Biochemistry and Molecular Biology285:42, s. 32038-320460021-92581083-351X
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