Cleavage of protein S by a platelet membrane protease

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Abstract

Protein S is a vitamin K-dependent glycoprotein cofactor to the serine protease, activated protein C. In this study we demonstrate that 125I-protein S bound to unstimulated platelets in a time- and calcium-dependent saturable reaction. Half-maximal binding occurred at a protein S concentration of 10 nM, with ~ 1,100 binding sites per platelet. The binding of protein S to platelets was followed by rapid cleavage of the protein mediated by a protease confined to the platelet membrane. The membrane protease was Ca++-dependent, inhibited by high concentrations of diisopropyl fluorophosphate, but was resistant to a variety of other protease inhibitors. Functional studies demonstrated that the cleavage of protein S was associated with complete loss of cofactor anticoagulant activity. We conclude that protein S binds to platelets and is inactivated by a novel Ca++-dependent membrane protease. This may represent a physiological reaction that regulates the activity of protein S.

Original languageEnglish
Pages (from-to)374-379
Number of pages6
JournalJournal of Clinical Investigation
Volume79
Issue number2
Publication statusPublished - 1987

Cite this

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title = "Cleavage of protein S by a platelet membrane protease",
abstract = "Protein S is a vitamin K-dependent glycoprotein cofactor to the serine protease, activated protein C. In this study we demonstrate that 125I-protein S bound to unstimulated platelets in a time- and calcium-dependent saturable reaction. Half-maximal binding occurred at a protein S concentration of 10 nM, with ~ 1,100 binding sites per platelet. The binding of protein S to platelets was followed by rapid cleavage of the protein mediated by a protease confined to the platelet membrane. The membrane protease was Ca++-dependent, inhibited by high concentrations of diisopropyl fluorophosphate, but was resistant to a variety of other protease inhibitors. Functional studies demonstrated that the cleavage of protein S was associated with complete loss of cofactor anticoagulant activity. We conclude that protein S binds to platelets and is inactivated by a novel Ca++-dependent membrane protease. This may represent a physiological reaction that regulates the activity of protein S.",
author = "Mitchell, {C. A.} and Salem, {H. H.}",
year = "1987",
language = "English",
volume = "79",
pages = "374--379",
journal = "Journal of Clinical Investigation",
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Cleavage of protein S by a platelet membrane protease. / Mitchell, C. A.; Salem, H. H.

In: Journal of Clinical Investigation, Vol. 79, No. 2, 1987, p. 374-379.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - Cleavage of protein S by a platelet membrane protease

AU - Mitchell, C. A.

AU - Salem, H. H.

PY - 1987

Y1 - 1987

N2 - Protein S is a vitamin K-dependent glycoprotein cofactor to the serine protease, activated protein C. In this study we demonstrate that 125I-protein S bound to unstimulated platelets in a time- and calcium-dependent saturable reaction. Half-maximal binding occurred at a protein S concentration of 10 nM, with ~ 1,100 binding sites per platelet. The binding of protein S to platelets was followed by rapid cleavage of the protein mediated by a protease confined to the platelet membrane. The membrane protease was Ca++-dependent, inhibited by high concentrations of diisopropyl fluorophosphate, but was resistant to a variety of other protease inhibitors. Functional studies demonstrated that the cleavage of protein S was associated with complete loss of cofactor anticoagulant activity. We conclude that protein S binds to platelets and is inactivated by a novel Ca++-dependent membrane protease. This may represent a physiological reaction that regulates the activity of protein S.

AB - Protein S is a vitamin K-dependent glycoprotein cofactor to the serine protease, activated protein C. In this study we demonstrate that 125I-protein S bound to unstimulated platelets in a time- and calcium-dependent saturable reaction. Half-maximal binding occurred at a protein S concentration of 10 nM, with ~ 1,100 binding sites per platelet. The binding of protein S to platelets was followed by rapid cleavage of the protein mediated by a protease confined to the platelet membrane. The membrane protease was Ca++-dependent, inhibited by high concentrations of diisopropyl fluorophosphate, but was resistant to a variety of other protease inhibitors. Functional studies demonstrated that the cleavage of protein S was associated with complete loss of cofactor anticoagulant activity. We conclude that protein S binds to platelets and is inactivated by a novel Ca++-dependent membrane protease. This may represent a physiological reaction that regulates the activity of protein S.

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M3 - Article

VL - 79

SP - 374

EP - 379

JO - Journal of Clinical Investigation

JF - Journal of Clinical Investigation

SN - 0021-9738

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ER -